ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.957C>A (p.His319Gln)

dbSNP: rs111033792
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000003801 SCV000479771 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2017-04-27 criteria provided, single submitter clinical testing The GALT c.957C>A (p.His319Gln) variant has been reported in four patient studies in which it is identified in a total of six individuals with galactosemia, including one in a homozygous state, three in a compound heterozygous state, and two in a heterozygous state without a second identified variant (Reichardt et al., 1993; Maceratesi et al., 1996; Singh et al., 2012; Schadewaldt et al., 2014). The p.His319Gln variant was absent from 178 control alleles and is reported at a frequency of 0.00001 in the European (non-Finnish) population of the Exome Aggregation Consortium, but this is based on one allele only in an area of good coverage so the variant is presumed to be rare. In a study by Reichardt et al. (1993), expression analysis of the variant in COS7 cells showed undetectable enzyme activity. Further analysis of transfected cells carrying the p.His319Gln variant failed to detect appreciable amounts of protein whilst having a high level of mRNA, suggesting the p.His319Gln variant encodes an unstable polypeptide. The residue resides in a domain that is conserved in E.coli and yeast and is located in the metal binding site of GALT (McCorvie et al. 2016). Schadewalt et al. (2014) and Singh et al. (2012) also found low levels of GALT enzyme activity in patients with the p.His319Gln variant ranging from 18% to less than 1.5% of control levels. Based on the evidence, the p.His319Gln variant is classified as pathogenic for galactosemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000003801 SCV000821132 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2023-09-27 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 319 of the GALT protein (p.His319Gln). This variant is present in population databases (rs111033792, gnomAD 0.0009%). This missense change has been observed in individual(s) with galactose-1-phosphate uridylyltransferase deficiency (PMID: 8499924, 8956044, 22944367, 23022339, 25268296). ClinVar contains an entry for this variant (Variation ID: 3617). 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. Experimental studies have shown that this missense change affects GALT function (PMID: 8499924). For these reasons, this variant has been classified as Pathogenic.
Eurofins Ntd Llc (ga) RCV000727567 SCV000854805 pathogenic not provided 2017-12-13 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000727567 SCV001246078 pathogenic not provided 2018-08-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV000003801 SCV004198504 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2023-10-07 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000727567 SCV004226600 pathogenic not provided 2022-10-05 criteria provided, single submitter clinical testing PP3, PP4, PM2, PM3, PS3, PS4_moderate
OMIM RCV000003801 SCV000023966 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 1993-03-01 no assertion criteria provided literature only
Counsyl RCV000003801 SCV000788876 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2016-12-21 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.