ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.4051C>T (p.Gln1351Ter)
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.4051C>T (p.Gln1351Ter)
Variation ID: 188947 Accession: VCV000188947.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q14.3 13: 51935666 (GRCh38) [ NCBI UCSC ] 13: 52509802 (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 29, 2015 Feb 14, 2024 Dec 9, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000053.4:c.4051C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Gln1351Ter nonsense NM_001005918.3:c.3430C>T NP_001005918.1:p.Gln1144Ter nonsense NM_001243182.2:c.3718C>T NP_001230111.1:p.Gln1240Ter nonsense NM_001330578.2:c.3817C>T NP_001317507.1:p.Gln1273Ter nonsense NM_001330579.2:c.3799C>T NP_001317508.1:p.Gln1267Ter nonsense NC_000013.11:g.51935666G>A NC_000013.10:g.52509802G>A NG_008806.1:g.80829C>T - Protein change
- Q1351*, Q1144*, Q1240*, Q1267*, Q1273*
- Other names
- p.Gln1351*
- Canonical SPDI
- NC_000013.11:51935665:G: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
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00001
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
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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
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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Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Dec 9, 2023 | RCV000169321.16 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jun 14, 2023 | RCV000726684.12 |
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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Pathogenic
(Oct 04, 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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Eurofins Ntd Llc (ga)
Accession: SCV000702098.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Dec 01, 2017)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000883429.1
First in ClinVar: Dec 15, 2018 Last updated: Dec 15, 2018 |
Comment:
The ATP7B c.4051C>T, p.Gln1351Ter variant (rs786204578) has been reported in multiple individuals with Wilson's disease (Folhoffer 2007, Genschel 2000, Gromadzka 2005, Moller 2011, Vrabelova 2005). … (more)
The ATP7B c.4051C>T, p.Gln1351Ter variant (rs786204578) has been reported in multiple individuals with Wilson's disease (Folhoffer 2007, Genschel 2000, Gromadzka 2005, Moller 2011, Vrabelova 2005). It is listed in ClinVar (Variation ID: 188947), and observed once in the Genome Aggregation Database general population database (1/242182 alleles). The variant introduces a premature termination codon, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, the variant is classified as pathogenic. References: Folhoffer A et al. Novel mutations of the ATP7B gene among 109 Hungarian patients with Wilson's disease. Eur J Gastroenterol Hepatol. 2007; 19(2):105-11. Genschel J et al. Three novel mutations (P760L, L1305P, Q1351Stop) causing Wilson disease. Hum Mutat. 2001; 17(2):156. 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; 68(6):524-32. Moller L et al. Clinical presentation and mutations in Danish patients with Wilson disease. Eur J Hum Genet. 2011; 19(9):935-41. Vrabelova S et al. Mutation analysis of the ATP7B gene and genotype/phenotype correlation in 227 patients with Wilson disease. Mol Genet Metab. 2005; 86(1-2):277-85. (less)
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Pathogenic
(Oct 06, 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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918590.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: The ATP7B c.4051C>T (p.Gln1351X) variant results in a premature termination codon, predicted to cause a truncated or absent ATP7B protein due to nonsense … (more)
Variant summary: The ATP7B c.4051C>T (p.Gln1351X) variant results in a premature termination codon, predicted to cause a truncated or absent ATP7B protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 1/242182 control chromosomes at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). Multiple publications cite the variant in compound heterozygote and homozygote affected individuals. A clinical diagnostic laboratory classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic. (less)
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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: SCV001977214.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Pathogenic
(May 09, 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: SCV002798005.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Sep 05, 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: SCV004216342.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jun 14, 2023)
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004226639.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP4, PM2, PM3, PS4_moderate, PVS1_strong
Number of individuals with the variant: 1
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Pathogenic
(Dec 09, 2023)
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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: SCV001232297.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln1351*) 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.Gln1351*) 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 present in population databases (rs786204578, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 11180609, 16283883, 26799313). ClinVar contains an entry for this variant (Variation ID: 188947). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Sep 09, 2016)
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no assertion criteria provided
Method: clinical testing
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Wilson disease
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220652.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 23, 2019 |
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Pathogenic
(Sep 16, 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: SCV001455572.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Pathogenic
(Nov 02, 2023)
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no assertion criteria provided
Method: clinical testing
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Wilson disease
Affected status: yes
Allele origin:
germline
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Zotz-Klimas Genetics Lab, MVZ Zotz Klimas
Accession: SCV004101121.1
First in ClinVar: Nov 11, 2023 Last updated: Nov 11, 2023 |
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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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ATP7B variant spectrum in a French pediatric Wilson disease cohort. | Couchonnal E | European journal of medical genetics | 2021 | PMID: 34400371 |
ATP7B Gene Mutations in Croatian Patients with Wilson Disease. | Ljubić H | Genetic testing and molecular biomarkers | 2016 | PMID: 26799313 |
Gastrointestinal side effects in children with Wilson's disease treated with zinc sulphate. | Wiernicka A | World journal of gastroenterology | 2013 | PMID: 23885147 |
Molecular analysis of Wilson patients: direct sequencing and MLPA analysis in the ATP7B gene and Atox1 and COMMD1 gene analysis. | Bost M | Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) | 2012 | PMID: 22677543 |
Clinical presentation and mutations in Danish patients with Wilson disease. | Møller LB | European journal of human genetics : EJHG | 2011 | PMID: 21610751 |
Critical roles for the COOH terminus of the Cu-ATPase ATP7B in protein stability, trans-Golgi network retention, copper sensing, and retrograde trafficking. | Braiterman L | American journal of physiology. Gastrointestinal and liver physiology | 2011 | PMID: 21454443 |
Novel mutations of the ATP7B gene among 109 Hungarian patients with Wilson's disease. | Folhoffer A | European journal of gastroenterology & hepatology | 2007 | PMID: 17272994 |
Revised King's College score for liver transplantation in adult patients with Wilson's disease. | Petrasek J | Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society | 2007 | PMID: 17154398 |
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 |
Three novel mutations (P760L, L1305P, Q1351Stop) causing Wilson disease. | Genschel J | Human mutation | 2001 | PMID: 11180609 |
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 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATP7B | - | - | - | - |
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Text-mined citations for rs786204578 ...
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.