ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.754C>A (p.Gln252Lys)

dbSNP: rs1564101859
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781407 SCV000919409 uncertain significance not specified 2018-12-27 criteria provided, single submitter clinical testing Variant summary: GALT c.754C>A (p.Gln252Lys) results in a conservative amino acid change in the C-terminal domain (IPR005850) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245788 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.754C>A in individuals affected with Galactosemia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001347764 SCV001542039 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2024-06-28 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 252 of the GALT protein (p.Gln252Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GALT-related conditions. ClinVar contains an entry for this variant (Variation ID: 633238). 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001347764 SCV005876546 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2024-02-22 criteria provided, single submitter clinical testing The GALT c.754C>A; p.Gln252Lys variant (rs1564101859), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 633238). This variant is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.838). However, given the lack of clinical and functional data, the significance of this variant is uncertain at this time.
Natera, Inc. RCV001825535 SCV002085231 uncertain significance Galactosemia 2018-11-30 no assertion criteria provided clinical testing

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