This missense variant replaces glutamine with histidine at codon 1372 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATP7B-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.4116G>C (p.Gln1372His)
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.
(2)
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.
Uncertain significance
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000053.4(ATP7B):c.4116G>C (p.Gln1372His)
Variation ID: 2774736 Accession: VCV002774736.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q14.3 13: 51935601 (GRCh38) [ NCBI UCSC ] 13: 52509737 (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 Feb 14, 2024 Apr 20, 2024 Jul 19, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000053.4:c.4116G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Gln1372His missense NM_001005918.3:c.3495G>C NP_001005918.1:p.Gln1165His missense NM_001243182.2:c.3783G>C NP_001230111.1:p.Gln1261His missense NM_001330578.2:c.3882G>C NP_001317507.1:p.Gln1294His missense NM_001330579.2:c.3864G>C NP_001317508.1:p.Gln1288His missense NM_001406511.1:c.4116G>C NP_001393440.1:p.Gln1372His missense NM_001406512.1:c.4116G>C NP_001393441.1:p.Gln1372His missense NM_001406513.1:c.4110G>C NP_001393442.1:p.Gln1370His missense NM_001406514.1:c.4083G>C NP_001393443.1:p.Gln1361His missense NM_001406515.1:c.4062G>C NP_001393444.1:p.Gln1354His missense NM_001406516.1:c.4062G>C NP_001393445.1:p.Gln1354His missense NM_001406517.1:c.4020G>C NP_001393446.1:p.Gln1340His missense NM_001406518.1:c.4020G>C NP_001393447.1:p.Gln1340His missense NM_001406519.1:c.3981G>C NP_001393448.1:p.Gln1327His missense NM_001406520.1:c.3972G>C NP_001393449.1:p.Gln1324His missense NM_001406521.1:c.3972G>C NP_001393450.1:p.Gln1324His missense NM_001406522.1:c.3972G>C NP_001393451.1:p.Gln1324His missense NM_001406523.1:c.3933G>C NP_001393452.1:p.Gln1311His missense NM_001406524.1:c.3939G>C NP_001393453.1:p.Gln1313His missense NM_001406525.1:c.3921G>C NP_001393454.1:p.Gln1307His missense NM_001406526.1:c.3912G>C NP_001393455.1:p.Gln1304His missense NM_001406527.1:c.3882G>C NP_001393456.1:p.Gln1294His missense NM_001406528.1:c.3882G>C NP_001393457.1:p.Gln1294His missense NM_001406530.1:c.3876G>C NP_001393459.1:p.Gln1292His missense NM_001406531.1:c.3864G>C NP_001393460.1:p.Gln1288His missense NM_001406532.1:c.3864G>C NP_001393461.1:p.Gln1288His missense NM_001406534.1:c.3828G>C NP_001393463.1:p.Gln1276His missense NM_001406535.1:c.3786G>C NP_001393464.1:p.Gln1262His missense NM_001406536.1:c.3786G>C NP_001393465.1:p.Gln1262His missense NM_001406537.1:c.3777G>C NP_001393466.1:p.Gln1259His missense NM_001406538.1:c.3738G>C NP_001393467.1:p.Gln1246His missense NM_001406539.1:c.3687G>C NP_001393468.1:p.Gln1229His missense NM_001406540.1:c.3669G>C NP_001393469.1:p.Gln1223His missense NM_001406541.1:c.3630G>C NP_001393470.1:p.Gln1210His missense NM_001406542.1:c.3630G>C NP_001393471.1:p.Gln1210His missense NM_001406543.1:c.3624G>C NP_001393472.1:p.Gln1208His missense NM_001406544.1:c.3534G>C NP_001393473.1:p.Gln1178His missense NM_001406545.1:c.3468G>C NP_001393474.1:p.Gln1156His missense NM_001406546.1:c.3435G>C NP_001393475.1:p.Gln1145His missense NM_001406547.1:c.3273G>C NP_001393476.1:p.Gln1091His missense NM_001406548.1:c.2826G>C NP_001393477.1:p.Gln942His missense NC_000013.11:g.51935601C>G NC_000013.10:g.52509737C>G NG_008806.1:g.80894G>C - Protein change
- Q1178H, Q1210H, Q1229H, Q1246H, Q1304H, Q1313H, Q1372H, Q1091H, Q1311H, Q1354H, Q1223H, Q1288H, Q1307H, Q1324H, Q1361H, Q1370H, Q942H, Q1145H, Q1156H, Q1165H, Q1208H, Q1259H, Q1261H, Q1262H, Q1276H, Q1292H, Q1294H, Q1327H, Q1340H
- Other names
- -
- Canonical SPDI
- NC_000013.11:51935600:C:G
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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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- 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. |
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| 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. |
|---|---|---|---|---|
| Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Jul 19, 2023 | RCV003504083.3 |
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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|---|---|---|---|---|---|
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Uncertain significance
(May 24, 2023)
|
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: SCV004361953.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces glutamine with histidine at codon 1372 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces glutamine with histidine at codon 1372 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATP7B-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
|
|
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Uncertain Significance
(Jul 19, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Wilson disease
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004833980.1
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)
|
Comment:
This missense variant replaces glutamine with histidine at codon 1372 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces glutamine with histidine at codon 1372 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATP7B-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 1
|
Comment:
Comment:
This missense variant replaces glutamine with histidine at codon 1372 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATP7B-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
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 missense variant replaces glutamine with histidine at codon 1372 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATP7B-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
This missense variant replaces glutamine with histidine at codon 1372 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATP7B-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 08, 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.