This sequence change creates a premature translational stop signal (p.Gly451Valfs*47) 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 variant has not been reported in the literature in individuals affected with ATP7B-related conditions. For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.1352del (p.Gly451fs)
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.
(1)
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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.
Pathogenic
1
criteria provided, single submitter
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.1352del (p.Gly451fs)
Variation ID: 2702550 Accession: VCV002702550.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 13q14.3 13: 51970683 (GRCh38) [ NCBI UCSC ] 13: 52544819 (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 Feb 14, 2024 Dec 12, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000053.4:c.1352del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Gly451fs frameshift NM_001005918.3:c.1352del NP_001005918.1:p.Gly451fs frameshift NM_001243182.2:c.1019del NP_001230111.1:p.Gly340fs frameshift NM_001330578.2:c.1352del NP_001317507.1:p.Gly451fs frameshift NM_001330579.2:c.1352del NP_001317508.1:p.Gly451fs frameshift NM_001406511.1:c.1352del NP_001393440.1:p.Gly451fs frameshift NM_001406512.1:c.1352del NP_001393441.1:p.Gly451fs frameshift NM_001406513.1:c.1352del NP_001393442.1:p.Gly451fs frameshift NM_001406514.1:c.1352del NP_001393443.1:p.Gly451fs frameshift NM_001406515.1:c.1352del NP_001393444.1:p.Gly451fs frameshift NM_001406516.1:c.1352del NP_001393445.1:p.Gly451fs frameshift NM_001406517.1:c.1256del NP_001393446.1:p.Gly419fs frameshift NM_001406518.1:c.1256del NP_001393447.1:p.Gly419fs frameshift NM_001406519.1:c.1352del NP_001393448.1:p.Gly451fs frameshift NM_001406520.1:c.1352del NP_001393449.1:p.Gly451fs frameshift NM_001406521.1:c.1352del NP_001393450.1:p.Gly451fs frameshift NM_001406522.1:c.1352del NP_001393451.1:p.Gly451fs frameshift NM_001406523.1:c.1352del NP_001393452.1:p.Gly451fs frameshift NM_001406524.1:c.1352del NP_001393453.1:p.Gly451fs frameshift NM_001406525.1:c.1352del NP_001393454.1:p.Gly451fs frameshift NM_001406526.1:c.1352del NP_001393455.1:p.Gly451fs frameshift NM_001406527.1:c.1352del NP_001393456.1:p.Gly451fs frameshift NM_001406528.1:c.1352del NP_001393457.1:p.Gly451fs frameshift NM_001406530.1:c.1256del NP_001393459.1:p.Gly419fs frameshift NM_001406531.1:c.1352del NP_001393460.1:p.Gly451fs frameshift NM_001406532.1:c.1352del NP_001393461.1:p.Gly451fs frameshift NM_001406534.1:c.1352del NP_001393463.1:p.Gly451fs frameshift NM_001406535.1:c.1352del NP_001393464.1:p.Gly451fs frameshift NM_001406536.1:c.1256del NP_001393465.1:p.Gly419fs frameshift NM_001406537.1:c.1352del NP_001393466.1:p.Gly451fs frameshift NM_001406538.1:c.1352del NP_001393467.1:p.Gly451fs frameshift NM_001406539.1:c.923del NP_001393468.1:p.Gly308fs frameshift NM_001406540.1:c.1352del NP_001393469.1:p.Gly451fs frameshift NM_001406541.1:c.1352del NP_001393470.1:p.Gly451fs frameshift NM_001406542.1:c.1352del NP_001393471.1:p.Gly451fs frameshift NM_001406543.1:c.1256del NP_001393472.1:p.Gly419fs frameshift NM_001406544.1:c.1256del NP_001393473.1:p.Gly419fs frameshift NM_001406545.1:c.1352del NP_001393474.1:p.Gly451fs frameshift NM_001406546.1:c.1352del NP_001393475.1:p.Gly451fs frameshift NM_001406547.1:c.1352del NP_001393476.1:p.Gly451fs frameshift NM_001406548.1:c.1285+3252del intron variant NC_000013.11:g.51970684del NC_000013.10:g.52544820del NG_008806.1:g.45812del - Protein change
- G451fs, G308fs, G340fs, G419fs
- Other names
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- Canonical SPDI
- NC_000013.11:51970682:CC: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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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 | ||
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| 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 |
2916 | 3060 | |
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 (1) |
criteria provided, single submitter
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Dec 12, 2023 | RCV003503512.2 |
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
(Dec 12, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004367438.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gly451Valfs*47) 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.Gly451Valfs*47) 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 variant has not been reported in the literature in individuals affected with ATP7B-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
|
Comment:
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 sequence change creates a premature translational stop signal (p.Gly451Valfs*47) 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 variant has not been reported in the literature in individuals affected with ATP7B-related conditions. For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 this variant ...
HelpRecord last updated Sep 30, 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.