ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.3784G>T (p.Val1262Phe)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000053.4(ATP7B):c.3784G>T (p.Val1262Phe)
Variation ID: 550902 Accession: VCV000550902.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q14.3 13: 51937595 (GRCh38) [ NCBI UCSC ] 13: 52511731 (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 Aug 5, 2018 Feb 14, 2024 Jan 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000053.4:c.3784G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Val1262Phe missense NM_001005918.3:c.3163G>T NP_001005918.1:p.Val1055Phe missense NM_001243182.2:c.3451G>T NP_001230111.1:p.Val1151Phe missense NM_001330578.2:c.3550G>T NP_001317507.1:p.Val1184Phe missense NM_001330579.2:c.3532G>T NP_001317508.1:p.Val1178Phe missense NC_000013.11:g.51937595C>A NC_000013.10:g.52511731C>A NG_008806.1:g.78900G>T - Protein change
- V1262F, V1055F, V1151F, V1184F, V1178F
- Other names
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- Canonical SPDI
- NC_000013.11:51937594:C:A
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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.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
- 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 | ||
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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 |
2572 | 2712 |
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
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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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Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jan 25, 2024 | RCV000665788.11 |
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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Likely pathogenic
(Mar 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000789962.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Likely pathogenic
(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: SCV001977234.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Pathogenic
(Mar 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004216466.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jan 25, 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: SCV001235665.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1262 of the ATP7B protein (p.Val1262Phe). … (more)
This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1262 of the ATP7B protein (p.Val1262Phe). This variant is present in population databases (rs769484789, gnomAD 0.003%). This missense change has been observed in individual(s) with Wilson's disease (PMID: 10544227, 20485189; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 550902). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATP7B protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ATP7B function (PMID: 19937698). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 18, 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: SCV002086795.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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The Challenges of Diagnosing and Following Wilson Disease in the Presence of Proteinuria. | Khan S | Pediatric gastroenterology, hepatology & nutrition | 2016 | PMID: 27437191 |
Laser ablation inductively coupled plasma mass spectrometry imaging of metals in experimental and clinical Wilson's disease. | Boaru SG | Journal of cellular and molecular medicine | 2015 | PMID: 25704483 |
Zinc monotherapy is effective in Wilson's disease patients with mild liver disease diagnosed in childhood: a retrospective study. | Ranucci G | Orphanet journal of rare diseases | 2014 | PMID: 24661374 |
Outcome and development of symptoms after orthotopic liver transplantation for Wilson disease. | Weiss KH | Clinical transplantation | 2013 | PMID: 24118554 |
Long-term follow-up of Wilson disease: natural history, treatment, mutations analysis and phenotypic correlation. | Bruha R | Liver international : official journal of the International Association for the Study of the Liver | 2011 | PMID: 20958917 |
Homozygous mutations in the conserved ATP hinge region of the Wilson disease gene: association with liver disease. | Barada K | Journal of clinical gastroenterology | 2010 | PMID: 20485189 |
Reduced expression of ATP7B affected by Wilson disease-causing mutations is rescued by pharmacological folding chaperones 4-phenylbutyrate and curcumin. | van den Berghe PV | Hepatology (Baltimore, Md.) | 2009 | PMID: 19937698 |
Mutation analysis in patients of Mediterranean descent with Wilson disease: identification of 19 novel mutations. | Loudianos G | Journal of medical genetics | 1999 | PMID: 10544227 |
Text-mined citations for rs769484789 ...
HelpRecord last updated Feb 20, 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.