This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1074 of the ATP7B protein (p.Ala1074Thr). 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. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.3220G>A (p.Ala1074Thr)
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.
Conflicting classifications of pathogenicity
Pathogenic(1); Uncertain significance(1)
Pathogenic(1); Uncertain significance(1)
2
criteria provided, conflicting classifications
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.3220G>A (p.Ala1074Thr)
Variation ID: 2166762 Accession: VCV002166762.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q14.3 13: 51944132 (GRCh38) [ NCBI UCSC ] 13: 52518268 (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 8, 2023 Jun 17, 2024 Mar 15, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000053.4:c.3220G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Ala1074Thr missense NM_001005918.3:c.2599G>A NP_001005918.1:p.Ala867Thr missense NM_001243182.2:c.2887G>A NP_001230111.1:p.Ala963Thr missense NM_001330578.2:c.2986G>A NP_001317507.1:p.Ala996Thr missense NM_001330579.2:c.2968G>A NP_001317508.1:p.Ala990Thr missense NM_001406511.1:c.3220G>A NP_001393440.1:p.Ala1074Thr missense NM_001406512.1:c.3220G>A NP_001393441.1:p.Ala1074Thr missense NM_001406513.1:c.3214G>A NP_001393442.1:p.Ala1072Thr missense NM_001406514.1:c.3187G>A NP_001393443.1:p.Ala1063Thr missense NM_001406515.1:c.3166G>A NP_001393444.1:p.Ala1056Thr missense NM_001406516.1:c.3166G>A NP_001393445.1:p.Ala1056Thr missense NM_001406517.1:c.3124G>A NP_001393446.1:p.Ala1042Thr missense NM_001406518.1:c.3124G>A NP_001393447.1:p.Ala1042Thr missense NM_001406519.1:c.3085G>A NP_001393448.1:p.Ala1029Thr missense NM_001406520.1:c.3076G>A NP_001393449.1:p.Ala1026Thr missense NM_001406521.1:c.3076G>A NP_001393450.1:p.Ala1026Thr missense NM_001406522.1:c.3076G>A NP_001393451.1:p.Ala1026Thr missense NM_001406524.1:c.3043G>A NP_001393453.1:p.Ala1015Thr missense NM_001406525.1:c.3025G>A NP_001393454.1:p.Ala1009Thr missense NM_001406526.1:c.3220G>A NP_001393455.1:p.Ala1074Thr missense NM_001406527.1:c.2986G>A NP_001393456.1:p.Ala996Thr missense NM_001406528.1:c.2986G>A NP_001393457.1:p.Ala996Thr missense NM_001406530.1:c.2980G>A NP_001393459.1:p.Ala994Thr missense NM_001406531.1:c.2968G>A NP_001393460.1:p.Ala990Thr missense NM_001406532.1:c.2968G>A NP_001393461.1:p.Ala990Thr missense NM_001406534.1:c.2932G>A NP_001393463.1:p.Ala978Thr missense NM_001406535.1:c.2890G>A NP_001393464.1:p.Ala964Thr missense NM_001406536.1:c.2890G>A NP_001393465.1:p.Ala964Thr missense NM_001406537.1:c.2881G>A NP_001393466.1:p.Ala961Thr missense NM_001406538.1:c.2986G>A NP_001393467.1:p.Ala996Thr missense NM_001406539.1:c.2791G>A NP_001393468.1:p.Ala931Thr missense NM_001406540.1:c.2773G>A NP_001393469.1:p.Ala925Thr missense NM_001406541.1:c.2734G>A NP_001393470.1:p.Ala912Thr missense NM_001406542.1:c.2734G>A NP_001393471.1:p.Ala912Thr missense NM_001406543.1:c.2872G>A NP_001393472.1:p.Ala958Thr missense NM_001406544.1:c.2638G>A NP_001393473.1:p.Ala880Thr missense NM_001406545.1:c.2572G>A NP_001393474.1:p.Ala858Thr missense NM_001406546.1:c.2539G>A NP_001393475.1:p.Ala847Thr missense NM_001406547.1:c.2377G>A NP_001393476.1:p.Ala793Thr missense NM_001406548.1:c.1930G>A NP_001393477.1:p.Ala644Thr missense NC_000013.11:g.51944132C>T NC_000013.10:g.52518268C>T NG_008806.1:g.72363G>A - Protein change
- A1029T, A1056T, A644T, A880T, A925T, A931T, A990T, A1009T, A1072T, A847T, A912T, A958T, A961T, A994T, A1026T, A1042T, A1063T, A1074T, A858T, A963T, A978T, A996T, A1015T, A793T, A867T, A964T
- Other names
- -
- Canonical SPDI
- NC_000013.11:51944131:C:T
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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 |
2915 | 3059 | |
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. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Mar 15, 2024 | RCV003091933.3 |
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
(Aug 19, 2022)
|
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: SCV003482227.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1074 of the ATP7B protein (p.Ala1074Thr). … (more)
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1074 of the ATP7B protein (p.Ala1074Thr). 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. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
|
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Pathogenic
(Mar 15, 2024)
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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: SCV005053068.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
|
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 replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1074 of the ATP7B protein (p.Ala1074Thr). 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. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been 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 Sep 29, 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.