ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.857A>G (p.Tyr286Cys)

gnomAD frequency: 0.00003  dbSNP: rs367543262
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000022219 SCV000800554 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2017-06-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000022219 SCV002258508 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2023-12-05 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 286 of the GALT protein (p.Tyr286Cys). This variant is present in population databases (rs367543262, gnomAD 0.06%). This missense change has been observed in individual(s) with galactosemia (PMID: 15775761). ClinVar contains an entry for this variant (Variation ID: 38486). 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%. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000022219 SCV005394251 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2024-09-26 criteria provided, single submitter clinical testing Variant summary: GALT c.857A>G (p.Tyr286Cys) results in a non-conservative amino acid change located in the Galactose-1-phosphate uridyl transferase, C-terminal domain (IPR005850) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251490 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.857A>G has been reported in the presumed compound heterozygous state in the literature in at least 1 individual affected with Galactosemia (example, Zaffanello_2005). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity in patient erythrocytes (example, Zaffanello_2005). The following publication has been ascertained in the context of this evaluation (PMID: 15775761). ClinVar contains an entry for this variant (Variation ID: 38486). Based on the evidence outlined above, the variant was classified as likely pathogenic.

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