ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.626A>C (p.Tyr209Ser)

dbSNP: rs111033744
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000022168 SCV001575145 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2022-06-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Tyr209 amino acid residue in GALT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10399107, 11397328, 16540753). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 25232). This missense change has been observed in individual(s) with classic galactosemia (PMID: 16765930, 22944367, 34030713). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 209 of the GALT protein (p.Tyr209Ser).
Baylor Genetics RCV000022168 SCV004198560 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2023-11-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000022168 SCV005380609 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2024-08-12 criteria provided, single submitter clinical testing Variant summary: GALT c.626A>C (p.Tyr209Ser) 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 251482 control chromosomes. c.626A>C has been reported in the literature in individuals affected with Galactosemia (examples: Zekanowski_1999, Mirzajani_2006, Boutron_2012). These data indicate that the variant is likely to be associated with disease. A different variant affecting the same codon has been classified as pathogenic by our lab (c.626A>G, p.Tyr209Cys), supporting the critical relevance of codon 209 to GALT protein function. The following publications have been ascertained in the context of this evaluation (PMID: 16765930, 22944367, 10399107). ClinVar contains an entry for this variant (Variation ID: 25232). Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV001826497 SCV002085222 likely pathogenic Galactosemia 2020-12-28 no assertion criteria provided clinical testing

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