Submissions for variant NM_015046.7(SETX):c.5473A>G (p.Thr1825Ala)

gnomAD frequency: 0.00051  dbSNP: rs151046729

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000821447	SCV000962203	likely benign	Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	2024-01-18	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000992944	SCV001145561	likely benign	not provided	2019-06-11	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001167265	SCV001329736	likely benign	Amyotrophic lateral sclerosis type 4	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001167266	SCV001329737	uncertain significance	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics	RCV002345897	SCV002649838	uncertain significance	Inborn genetic diseases	2019-09-10	criteria provided, single submitter	clinical testing	The p.T1825A variant (also known as c.5473A>G), located in coding exon 10 of the SETX gene, results from an A to G substitution at nucleotide position 5473. The threonine at codon 1825 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant juvenile amyotrophic lateral sclerosis 4 (ALS4); however, its contribution to the development of autosomal recessive spinocerebellar ataxia with axonal neuropathy 2 (SCAN2) is uncertain.
PreventionGenetics, part of Exact Sciences	RCV003965604	SCV004778916	likely benign	SETX-related condition	2023-08-28	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).