Submissions for variant NM_000155.4(GALT):c.404C>G (p.Ser135Trp)

dbSNP: rs111033690

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000022105	SCV000220928	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2014-12-02	criteria provided, single submitter	literature only
Invitae	RCV000022105	SCV002243714	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2023-07-21	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser135 amino acid residue in GALT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7887417, 22461411, 22944367, 27176039, 28065439). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 GALT protein function. ClinVar contains an entry for this variant (Variation ID: 25172). This missense change has been observed in individual(s) with galactose-1-phosphate uridylyltransferase deficiency (PMID: 15841485). This variant is present in population databases (rs111033690, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 135 of the GALT protein (p.Ser135Trp).
Baylor Genetics	RCV000022105	SCV004198502	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2023-10-13	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001723584	SCV001953979	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001723584	SCV001971495	likely pathogenic	not provided		no assertion criteria provided	clinical testing