ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.957C>A (p.His319Gln) (rs111033792)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000003801 SCV000788876 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2016-12-21 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727567 SCV000854805 pathogenic not provided 2017-12-13 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,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 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2017-12-07 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamine at codon 319 of the GALT protein (p.His319Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is present in population databases (rs111033792, ExAC 0.001%). This variant has been observed in several individuals affected with galactosemia (PMID: 25268296, 23022339, 22944367, 8956044, 8499924). ClinVar contains an entry for this variant (Variation ID: 3617). Studies of affected individuals have shown that this missense change results in undetectable GALT enzymatic activity in the blood (PMID: 8499924, 25268296). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000003801 SCV000023966 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 1993-03-01 no assertion criteria provided literature only
Research and Development, ARUP Laboratories RCV000003801 SCV000042925 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2012-12-04 no assertion criteria provided clinical testing Converted during submission to Pathogenic.

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.