Submissions for variant NM_003896.4(ST3GAL5):c.1247G>T (p.Arg416Leu)

gnomAD frequency: 0.00028  dbSNP: rs200683924

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000713526	SCV000232180	uncertain significance	not provided	2015-02-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000194785	SCV000249056	uncertain significance	not specified	2014-11-06	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000352472	SCV000432353	uncertain significance	GM3 synthase deficiency	2018-01-12	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.
Invitae	RCV000352472	SCV000835061	uncertain significance	GM3 synthase deficiency	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 416 of the ST3GAL5 protein (p.Arg416Leu). This variant is present in population databases (rs200683924, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with ST3GAL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 198500). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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.
Athena Diagnostics Inc	RCV000713526	SCV000844148	uncertain significance	not provided	2018-03-14	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000352472	SCV001520494	uncertain significance	GM3 synthase deficiency	2019-03-04	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV000713526	SCV001991661	uncertain significance	not provided	2019-07-29	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV000352472	SCV002796903	uncertain significance	GM3 synthase deficiency	2022-05-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002516803	SCV003686297	uncertain significance	Inborn genetic diseases	2022-12-14	criteria provided, single submitter	clinical testing	The c.1247G>T (p.R416L) alteration is located in exon 7 (coding exon 7) of the ST3GAL5 gene. This alteration results from a G to T substitution at nucleotide position 1247, causing the arginine (R) at amino acid position 416 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.