Submissions for variant NM_138422.4(ADAT3):c.383G>T (p.Arg128Leu)

gnomAD frequency: 0.00230  dbSNP: rs200992550

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000766848	SCV000618748	uncertain significance	not provided	2017-07-06	criteria provided, single submitter	clinical testing	The R128L variant in the ADAT3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R128L variant is observed in 4/2452 (0.16%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R128L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved and in silico analysis predicts this variant likely does not alter the protein structure/function. We interpret R128L as a variant of uncertain significance.
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	RCV000521772	SCV000864378	benign	not specified	2017-06-20	criteria provided, single submitter	clinical testing	BS1, BS2, BP4; This alteration has an allele frequency that is greater than expected for the associated disease, was seen in a healthy adult where full penetrance of the disorder is expected at an early age, and is predicted to be tolerated by multiple functional prediction tools.
Invitae	RCV000766848	SCV001122249	likely benign	not provided	2019-12-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000766848	SCV001747902	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	ADAT3: BS2
Genetic Services Laboratory, University of Chicago	RCV000521772	SCV002065917	likely benign	not specified	2018-04-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002525157	SCV003677852	likely benign	Inborn genetic diseases	2021-06-02	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003925560	SCV004742732	likely benign	ADAT3-related condition	2022-02-11	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).