Submissions for variant NM_020778.5(ALPK3):c.104C>T (p.Ala35Val)

gnomAD frequency: 0.01026  dbSNP: rs75088852

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000427018	SCV000525618	benign	not specified	2016-10-24	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001803731	SCV002047966	benign	Cardiomyopathy, familial hypertrophic 27	2024-07-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002058925	SCV002408257	benign	not provided	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002365512	SCV002666878	benign	Cardiovascular phenotype	2019-01-07	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Breakthrough Genomics, Breakthrough Genomics	RCV002058925	SCV005292003	benign	not provided		criteria provided, single submitter	not provided
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000427018	SCV005422004	benign	not specified	2024-10-28	criteria provided, single submitter	clinical testing	Variant summary: ALPK3 c.104C>T (p.Ala35Val) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.001 in 96092 control chromosomes, predominantly at a frequency of 0.035 within the African or African-American subpopulation in the gnomAD database with 5 homozygotes. The available data on variant occurrences in the general population suggests the variant may be a benign change. To our knowledge, no occurrence of c.104C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 384681). Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV004539836	SCV004771495	benign	ALPK3-related disorder	2019-03-12	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).