ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3221C>T (p.Ala1074Val)

gnomAD frequency: 0.00001  dbSNP: rs1206016866
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588068 SCV000694442 uncertain significance not provided 2016-07-19 criteria provided, single submitter clinical testing Variant summary: The ATP7B c.3221C>T (p.Ala1074Val) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. Ala1074 is highly conserved across species and is located in the P-type ATPase, cytoplasmic domain N of the Copper-transporting ATPase 2 protein. This variant was found in 1/130990 control chromosomes at a frequency of 0.0000076, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). The variant was identified in heterozygous state in one WD patient reported in the literature, but a variant in trans was not identified and co-segregation studies were not done, thus it is unclear if this variant is causal. Because of limited clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Fulgent Genetics, Fulgent Genetics RCV001829614 SCV002789053 uncertain significance Wilson disease 2022-05-13 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000588068 SCV004226656 likely pathogenic not provided 2023-03-28 criteria provided, single submitter clinical testing PP3, PP4, PM2, PM3
All of Us Research Program, National Institutes of Health RCV001829614 SCV004845398 uncertain significance Wilson disease 2024-04-16 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 1074 of the ATP7B protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with Wilson disease (PMID: 27022412, 23518715). This variant has been identified in 2/280730 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Natera, Inc. RCV001829614 SCV002086826 uncertain significance Wilson disease 2020-08-13 no assertion criteria provided clinical testing

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