Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000240853 | SCV004282470 | pathogenic | GM3 synthase deficiency | 2023-10-12 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 195 of the ST3GAL5 protein (p.Cys195Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of GM synthetase deficiency (PMID: 27232954). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 254245). 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. Experimental studies have shown that this missense change affects ST3GAL5 function (PMID: 30576498). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000240853 | SCV000299338 | pathogenic | GM3 synthase deficiency | 2016-09-16 | no assertion criteria provided | literature only |