Submissions for variant NM_000155.4(GALT):c.772C>T (p.Arg258Cys)

gnomAD frequency: 0.00001  dbSNP: rs368166217

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000493672	SCV000110073	pathogenic	not provided	2013-07-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000493672	SCV000582974	pathogenic	not provided	2023-06-09	criteria provided, single submitter	clinical testing	Identified in an individual with galactosemia who harbored a second variant in the GALT gene. This individual had >5% residual enzyme activity in erythrocytes and a Duarte-like isoelectric focusing banding pattern (Berry et al., 2000); Considered a milder GALT variant (Korner et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25087612, 30718057, 15633893, 30808388, 31194895, 10408771, 20008339, 23690308, 10960497, 17876724, 29350350, 11261429, 10384398, 31194252, 34426522, 35677809)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000493672	SCV000885498	likely pathogenic	not provided	2017-08-01	criteria provided, single submitter	clinical testing
Invitae	RCV000078235	SCV000931179	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2024-01-08	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 258 of the GALT protein (p.Arg258Cys). This variant is present in population databases (rs368166217, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of galactosemia (PMID: 10960497, 30718057; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 92522). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000078235	SCV003808590	uncertain significance	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2021-04-09	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000078235	SCV004198490	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2023-10-30	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000493672	SCV004226597	likely pathogenic	not provided	2023-03-13	criteria provided, single submitter	clinical testing	PP3, PP4, PM2, PM3, PS4_moderate
Counsyl	RCV000078235	SCV000800530	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2019-03-13	no assertion criteria provided	clinical testing
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000078235	SCV001469241	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2020-10-11	no assertion criteria provided	clinical testing