Submissions for variant NM_018834.6(MATR3):c.1132G>A (p.Ala378Thr)

gnomAD frequency: 0.00017  dbSNP: rs201075828

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000806815	SCV000946834	uncertain significance	Amyotrophic lateral sclerosis type 21	2023-12-10	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 378 of the MATR3 protein (p.Ala378Thr). This variant is present in population databases (rs201075828, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 32028661). ClinVar contains an entry for this variant (Variation ID: 651450). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Illumina Laboratory Services, Illumina	RCV000806815	SCV001319595	benign	Amyotrophic lateral sclerosis type 21	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV001683661	SCV001897914	benign	not provided	2020-01-30	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Revvity Omics, Revvity	RCV000806815	SCV003808294	uncertain significance	Amyotrophic lateral sclerosis type 21	2021-06-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001683661	SCV005041622	uncertain significance	not provided	2024-04-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004538106	SCV004117188	likely benign	MATR3-related disorder	2023-12-05	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).