ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.2785A>G (p.Ile929Val)
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.
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.
Uncertain significance(1); Benign(4); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000053.4(ATP7B):c.2785A>G (p.Ile929Val)
Variation ID: 193969 Accession: VCV000193969.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q14.3 13: 51949742 (GRCh38) [ NCBI UCSC ] 13: 52523878 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Mar 17, 2018 Mar 16, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000053.4:c.2785A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Ile929Val missense NM_001005918.3:c.2244+265A>G intron variant NM_001243182.2:c.2452A>G NP_001230111.1:p.Ile818Val missense NM_001330578.2:c.2551A>G NP_001317507.1:p.Ile851Val missense NM_001330579.2:c.2533A>G NP_001317508.1:p.Ile845Val missense NC_000013.11:g.51949742T>C NC_000013.10:g.52523878T>C NG_008806.1:g.66753A>G P35670:p.Ile929Val - Protein change
- I929V, I851V, I845V, I818V
- Other names
- -
- Canonical SPDI
- NC_000013.11:51949741:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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0.00140 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00038
Trans-Omics for Precision Medicine (TOPMed) 0.00069
The Genome Aggregation Database (gnomAD), exomes 0.00091
Exome Aggregation Consortium (ExAC) 0.00096
1000 Genomes Project 30x 0.00125
1000 Genomes Project 0.00140
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 | ||
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HI score
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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. |
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ATP7B | - | - |
GRCh38 GRCh37 |
2893 | 3035 |
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. |
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Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Oct 3, 2017 | RCV000174213.6 | |
Benign (1) |
criteria provided, single submitter
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Oct 6, 2016 | RCV000587605.3 | |
Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
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Jan 31, 2024 | RCV001081569.17 | |
ATP7B-related disorder
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Benign (1) |
criteria provided, single submitter
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Aug 9, 2019 | RCV003955024.1 |
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. |
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Benign
(Oct 06, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694430.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The ATP7B c.2785A>G (p.Ile929Val) variant involves the alteration of a non-conserved nucleotide. Ile929 is located in the transmembrane domain, is highly conserved across … (more)
Variant summary: The ATP7B c.2785A>G (p.Ile929Val) variant involves the alteration of a non-conserved nucleotide. Ile929 is located in the transmembrane domain, is highly conserved across species, and 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). However, yeast functional analyses showed no significant effect of this I929V. Additionally, this variant was found in 131/121316 control chromosomes (1 homozygote), predominantly observed in the East Asian subpopulation at a frequency of 0.0131243 (113/8610). This frequency is about 2 times the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, multiple sources, including a clinical diagnostic laboratory, a database, and publications, classified this variant as benign. Taken together, this variant is classified as Benign. (less)
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Benign
(Feb 23, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000225476.5
First in ClinVar: Jun 28, 2015 Last updated: May 03, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Likely benign
(Aug 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001977151.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Likely benign
(Sep 29, 2022)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV004362481.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000752280.7
First in ClinVar: May 28, 2018 Last updated: Feb 28, 2024 |
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Likely benign
(Oct 03, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000730409.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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)
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Uncertain significance
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001270798.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Benign
(Aug 09, 2019)
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criteria provided, single submitter
Method: clinical testing
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ATP7B-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004768097.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Benign
(Apr 15, 2020)
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no assertion criteria provided
Method: clinical testing
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Wilson disease
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001456173.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Spectrum and Classification of ATP7B Variants in a Large Cohort of Chinese Patients with Wilson's Disease Guides Genetic Diagnosis. | Dong Y | Theranostics | 2016 | PMID: 27022412 |
Acute Hepatic Phenotype of Wilson Disease: Clinical Features of Acute Episodes and Chronic Lesions Remaining in Survivors. | Hayashi H | Journal of clinical and translational hepatology | 2015 | PMID: 26807378 |
Biochemical staging of the chronic hepatic lesions of Wilson disease. | Katano Y | Nagoya journal of medical science | 2014 | PMID: 25130000 |
In silico investigation of the ATP7B gene: insights from functional prediction of non-synonymous substitution to protein structure. | Squitti R | Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine | 2014 | PMID: 24253677 |
Mutational analysis of ATP7B in north Chinese patients with Wilson disease. | Li K | Journal of human genetics | 2013 | PMID: 23235335 |
A structural model of the copper ATPase ATP7B to facilitate analysis of Wilson disease-causing mutations and studies of the transport mechanism. | Schushan M | Metallomics : integrated biometal science | 2012 | PMID: 22692182 |
Potential of the international scoring system for the diagnosis of Wilson disease to differentiate Japanese patients who need anti-copper treatment. | Tatsumi Y | Hepatology research : the official journal of the Japan Society of Hepatology | 2011 | PMID: 21707886 |
Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations. | Li XH | BMC medical genetics | 2011 | PMID: 21219664 |
Genetic polymorphisms of copper- and platinum drug-efflux transporters ATP7A and ATP7B in Japanese cancer patients. | Fukushima-Uesaka H | Drug metabolism and pharmacokinetics | 2009 | PMID: 20045993 |
Identification of novel ATP7B gene mutations and their functional roles in Korean patients with Wilson disease. | Park S | Human mutation | 2007 | PMID: 17587212 |
Mutation analysis and the correlation between genotype and phenotype of Arg778Leu mutation in chinese patients with Wilson disease. | Wu ZY | Archives of neurology | 2001 | PMID: 11405812 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATP7B | - | - | - | - |
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Text-mined citations for rs534960245 ...
HelpRecord last updated May 19, 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.