Submissions for variant NM_001605.3(AARS1):c.1632C>T (p.Asp544=)

gnomAD frequency: 0.00081  dbSNP: rs149425243

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000506789	SCV000602325	benign	not specified	2017-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001704658	SCV000729291	likely benign	not provided	2020-08-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000653968	SCV000775858	benign	Charcot-Marie-Tooth disease type 2	2023-12-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002461263	SCV002755351	likely benign	Inborn genetic diseases	2019-07-11	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000506789	SCV005394996	likely benign	not specified	2024-09-10	criteria provided, single submitter	clinical testing	Variant summary: AARS1 c.1632C>T alters a non-conserved nucleotide resulting in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00034 in 282878 control chromosomes in the gnomAD database, including 2 homozygotes. To our knowledge, no occurrence of c.1632C>T in individuals affected with Developmental and epileptic encephalopathy, 29 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 439344). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003960193	SCV004768744	likely benign	AARS1-related disorder	2019-02-18	no assertion criteria provided	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).