Submissions for variant NM_177924.5(ASAH1):c.1144G>A (p.Glu382Lys)

gnomAD frequency: 0.00024  dbSNP: rs148976489

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001163940	SCV001326030	uncertain significance	Farber lipogranulomatosis	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001338988	SCV001532700	uncertain significance	not provided	2024-01-24	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 382 of the ASAH1 protein (p.Glu382Lys). This variant is present in population databases (rs148976489, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with ASAH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 911466). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ASAH1 protein function with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mayo Clinic Laboratories, Mayo Clinic	RCV001338988	SCV001713449	uncertain significance	not provided	2019-12-27	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002480573	SCV002791069	uncertain significance	Spinal muscular atrophy-progressive myoclonic epilepsy syndrome; Farber lipogranulomatosis	2022-03-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001338988	SCV004164434	uncertain significance	not provided	2023-07-01	criteria provided, single submitter	clinical testing	ASAH1: PM2:Supporting