Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Revvity Omics, |
RCV001028020 | SCV002023669 | likely pathogenic | GM3 synthase deficiency | 2021-08-24 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002552014 | SCV003634389 | likely pathogenic | Inborn genetic diseases | 2022-06-29 | criteria provided, single submitter | clinical testing | The c.1024G>A (p.G342S) alteration is located in exon 7 (coding exon 7) of the ST3GAL5 gene. This alteration results from a G to A substitution at nucleotide position 1024, causing the glycine (G) at amino acid position 342 to be replaced by a serine (S). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported in the homozgyous and compound heterozygous states in patients with clinical features of salt and pepper developmental regression syndrome (Heide, 2022; Issa, 2020; Indellicato, 2019). This amino acid position is highly conserved in available vertebrate species. An in vitro assay showed that this alteration, when closed and expressed in HEK-293T cells, showed complete loss of GM3 synthase activity (Indellicato, 2019). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |
Labcorp Genetics |
RCV001028020 | SCV004551512 | pathogenic | GM3 synthase deficiency | 2023-05-25 | criteria provided, single submitter | clinical testing | 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 expected to disrupt ST3GAL5 protein function. ClinVar contains an entry for this variant (Variation ID: 828145). This missense change has been observed in individual(s) with ST3GAL5-related conditions (PMID: 30576498, 32404165, 34906476). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 342 of the ST3GAL5 protein (p.Gly342Ser). Experimental studies have shown that this missense change affects ST3GAL5 function (PMID: 30576498). For these reasons, this variant has been classified as Pathogenic. |
Biochemical Molecular Genetic Laboratory, |
RCV001028020 | SCV001190784 | pathogenic | GM3 synthase deficiency | 2020-02-05 | no assertion criteria provided | clinical testing |