ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.3843dup (p.Val1282fs)
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.3843dup (p.Val1282fs)
Variation ID: 958649 Accession: VCV000958649.26
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 13q14.3 13: 51937535-51937536 (GRCh38) [ NCBI UCSC ] 13: 52511671-52511672 (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 Jul 16, 2020 Apr 20, 2024 Jan 24, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000053.4:c.3843dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Val1282fs frameshift NM_000053.3:c.3843dupT NM_001005918.3:c.3222dup NP_001005918.1:p.Val1075fs frameshift NM_001243182.2:c.3510dup NP_001230111.1:p.Val1171fs frameshift NM_001330578.2:c.3609dup NP_001317507.1:p.Val1204fs frameshift NM_001330579.2:c.3591dup NP_001317508.1:p.Val1198fs frameshift NC_000013.11:g.51937536dup NC_000013.10:g.52511672dup NG_008806.1:g.78959dup - Protein change
- V1075fs, V1198fs, V1204fs, V1171fs, V1282fs
- Other names
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- Canonical SPDI
- NC_000013.11:51937535:A:AA
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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
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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
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
2850 | 2991 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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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 (7) |
criteria provided, multiple submitters, no conflicts
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Jan 24, 2024 | RCV001231852.19 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 1, 2023 | RCV003222267.7 |
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
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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
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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
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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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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: SCV001977230.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Pathogenic
(Nov 26, 2021)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002049143.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
Comment:
The ATP7B c.3843dupT; p.Val1282CysfsTer22 variant is reported in the literature in individuals with Wilson disease, including in at least one individual with an additional pathogenic … (more)
The ATP7B c.3843dupT; p.Val1282CysfsTer22 variant is reported in the literature in individuals with Wilson disease, including in at least one individual with an additional pathogenic variant (Hua 2016, Li 2011). The variant is reported in the ClinVar database (Variation ID: 958649) and is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by duplicating a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Loss of function is the pathogenic mechanism for Wilson disease and other frameshift variants in this region have been described in affected individuals and are considered pathogenic (Gromadzka 2005). Based on available information, the c.3843dupT; p.Val1282CysfsTer22 variant is considered to be pathogenic. References: Gromadzka G et al. Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease. Clin Genet. 2005 Dec;68(6):524-32. PMID: 16283883. Hua R et al Mutational analysis of ATP7B in Chinese Wilson disease patients. Am J Transl Res. 2016 Jun 15;8(6):2851-61. PMID: 27398169. Li XH et al. Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations. BMC Med Genet. 2011 Jan 11;12:6. PMID: 21219664. (less)
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Pathogenic
(Jul 18, 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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002570697.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
Variant summary: ATP7B c.3843dupT (p.Val1282CysfsX22) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: ATP7B c.3843dupT (p.Val1282CysfsX22) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251274 control chromosomes (gnomAD and publication data). c.3843dupT has been reported in the literature in individuals affected with Wilson Disease (Merle_2010, Li_2011, Hua_2016, Xiao_2021). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Feb 07, 2022)
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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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Fulgent Genetics, Fulgent Genetics
Accession: SCV002811668.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Sep 18, 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: SCV004216328.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jan 24, 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: SCV001404387.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Val1282Cysfs*22) in the ATP7B gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Val1282Cysfs*22) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 27398169). ClinVar contains an entry for this variant (Variation ID: 958649). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV003917288.7
First in ClinVar: Apr 23, 2023 Last updated: Apr 15, 2024 |
Comment:
ATP7B: PVS1, PM2, PM3, PS4:Moderate
Number of individuals with the variant: 1
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Pathogenic
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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Wilson disease
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004844591.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
This variant inserts 1 nucleotide in exon 18 of the ATP7B gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant inserts 1 nucleotide in exon 18 of the ATP7B gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in multiple individuals affected with Wilson disease (PMID: 21219664, 27398169, 34324271). One of these individuals has been confirmed to be compound heterozygous with another pathogenic variant in the same gene (PMID: 34324271). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATP7B function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
Number of individuals with the variant: 1
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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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Molecular analysis of 53 Chinese families with Wilson's disease: Six novel mutations identified. | Xiao Z | Molecular genetics & genomic medicine | 2021 | PMID: 34324271 |
Mutational analysis of ATP7B in Chinese Wilson disease patients. | Hua R | American journal of translational research | 2016 | PMID: 27398169 |
Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations. | Li XH | BMC medical genetics | 2011 | PMID: 21219664 |
Truncating mutations in the Wilson disease gene ATP7B are associated with very low serum ceruloplasmin oxidase activity and an early onset of Wilson disease. | Merle U | BMC gastroenterology | 2010 | PMID: 20082719 |
Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease. | Gromadzka G | Clinical genetics | 2005 | PMID: 16283883 |
Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation. | Buiakova OI | Human molecular genetics | 1999 | PMID: 10441329 |
Text-mined citations for rs1957043255 ...
HelpRecord last updated Apr 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.