This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.2973G>A (p.Thr991=)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(17)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Benign
17
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000053.4(ATP7B):c.2973G>A (p.Thr991=)
Variation ID: 35713 Accession: VCV000035713.38
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 13q14.3 13: 51946371 (GRCh38) [ NCBI UCSC ] 13: 52520507 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Sep 29, 2024 Feb 5, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000053.4:c.2973G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Thr991= synonymous NM_001005918.3:c.2352G>A NP_001005918.1:p.Thr784= synonymous NM_001243182.2:c.2640G>A NP_001230111.1:p.Thr880= synonymous NM_001330578.2:c.2739G>A NP_001317507.1:p.Thr913= synonymous NM_001330579.2:c.2721G>A NP_001317508.1:p.Thr907= synonymous NC_000013.11:g.51946371C>T NC_000013.10:g.52520507C>T NG_008806.1:g.70124G>A - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000013.11:51946370:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.02496 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 0.02496
1000 Genomes Project 30x 0.02561
Trans-Omics for Precision Medicine (TOPMed) 0.04524
The Genome Aggregation Database (gnomAD) 0.04852
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.05290
The Genome Aggregation Database (gnomAD), exomes 0.05375
Exome Aggregation Consortium (ExAC) 0.05802
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| ATP7B | - | - |
GRCh38 GRCh37 |
2918 | 3062 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Benign (8) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2024 | RCV000029362.31 | |
| Benign (7) |
criteria provided, multiple submitters, no conflicts
|
Jan 29, 2016 | RCV000078047.21 | |
| Benign (1) |
criteria provided, single submitter
|
Aug 10, 2016 | RCV002433471.2 | |
| Benign (1) |
criteria provided, single submitter
|
- | RCV004707855.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Benign
(Feb 08, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000192335.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
|
|
|
Benign
(Jan 29, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000517537.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
|
Benign
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000384664.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
|
Benign
(Jul 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV001750133.1
First in ClinVar: Jul 15, 2021 Last updated: Jul 15, 2021 |
Sex: mixed
|
|
|
benign
(Aug 18, 2011)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson Disease
(autosomal unknown)
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052009.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 11, 2022 |
Comment:
Converted during submission to Benign.
Observation 1:
Tissue: Blood
Observation 2:
Tissue: Blood
Observation 3:
Tissue: Blood
Observation 4:
Tissue: Blood
Observation 5:
Tissue: Blood
Observation 6:
Tissue: Blood
Observation 7:
Tissue: Blood
Observation 8:
Tissue: Blood
Observation 9:
Tissue: Blood
Observation 10:
Tissue: Blood
|
|
|
Benign
(Mar 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602598.9
First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023 |
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001726907.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
|
|
|
Benign
(Aug 10, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002746195.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000301708.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
|
Benign
(Jan 28, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000109885.8
First in ClinVar: Jan 17, 2014 Last updated: Mar 08, 2017 |
Number of individuals with the variant: 2
Sex: mixed
|
|
|
Benign
(Mar 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004362476.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
|
|
Benign
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004845448.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Number of individuals with the variant: 13540
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005230368.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Wilson disease
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001459712.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001809698.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001925905.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001930351.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
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Comment:
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
Converted during submission to Benign.
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
Converted during submission to Benign.
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Molecular pathogenesis of Wilson disease among Indians: a perspective on mutation spectrum in ATP7B gene, prevalent defects, clinical heterogeneity and implication towards diagnosis. | Gupta A | Cellular and molecular neurobiology | 2007 | PMID: 17823867 |
| Clinical and molecular characterization of Wilson disease in Spanish patients. | Brage A | Hepatology research : the official journal of the Japan Society of Hepatology | 2007 | PMID: 17300695 |
| Twenty-four novel mutations in Wilson disease patients of predominantly European ancestry. | Cox DW | Human mutation | 2005 | PMID: 16088907 |
| Mutation analysis of Wilson disease in the Spanish population -- identification of a prevalent substitution and eight novel mutations in the ATP7B gene. | Margarit E | Clinical genetics | 2005 | PMID: 15952988 |
| A study of Wilson disease mutations in Britain. | Curtis D | Human mutation | 1999 | PMID: 10502777 |
| Haplotype and mutation analysis in Greek patients with Wilson disease. | Loudianos G | European journal of human genetics : EJHG | 1998 | PMID: 9801873 |
| Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation, and functional analyses. | Shah AB | American journal of human genetics | 1997 | PMID: 9311736 |
| Efficient detection of mutations in Wilson disease by manifold sequencing. | Waldenström E | Genomics | 1996 | PMID: 8938442 |
| Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations. | Figus A | American journal of human genetics | 1995 | PMID: 8533760 |
| The Wilson disease gene: spectrum of mutations and their consequences. | Thomas GR | Nature genetics | 1995 | PMID: 7626145 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATP7B | - | - | - | - |
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Text-mined citations for rs1801246 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.