Submissions for variant NM_000053.4(ATP7B):c.3416C>G (p.Ala1139Gly)

gnomAD frequency: 0.00009  dbSNP: rs199924281

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001469712	SCV001673798	likely benign	Wilson disease	2024-06-13	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001820163	SCV002071365	uncertain significance	not specified	2019-10-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001469712	SCV004361965	uncertain significance	Wilson disease	2022-09-14	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with glycine at codon 1139 of the ATP7B protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with Wilson disease in the literature. This variant has been identified in 22/280964 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.
All of Us Research Program, National Institutes of Health	RCV001469712	SCV004845363	uncertain significance	Wilson disease	2024-09-23	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with glycine at codon 1139 of the ATP7B protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with Wilson disease in the literature. This variant has been identified in 22/280964 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.
GeneDx	RCV001579789	SCV005442938	uncertain significance	not provided	2024-07-05	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579789	SCV001808507	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001579789	SCV001970658	likely benign	not provided		no assertion criteria provided	clinical testing