ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.998G>A (p.Arg333Gln)

gnomAD frequency: 0.00001  dbSNP: rs111033808
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000022258 SCV000485649 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2016-01-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000022258 SCV000933081 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2023-12-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 333 of the GALT protein (p.Arg333Gln). This variant is present in population databases (rs111033808, gnomAD 0.01%). This missense change has been observed in individual(s) with classic galactosemia (PMID: 10573007, 25124065). ClinVar contains an entry for this variant (Variation ID: 38288). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GALT protein function. Experimental studies have shown that this missense change affects GALT function (PMID: 10573007). This variant disrupts the p.Arg333 amino acid residue in GALT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1897530, 10384398, 10399107, 18207281, 19181333, 25592817). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000022258 SCV001163253 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2024-03-24 criteria provided, single submitter clinical testing
GeneDx RCV001549598 SCV001769779 pathogenic not provided 2023-06-09 criteria provided, single submitter clinical testing Published functional studies in COS cells demonstrate 29% GALT activity compared to wild-type suggestive of a mild genetic variant (Hirokawa et al., 1999); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20008339, 25124065, 10408771, 10573007, 9686364, 31637888, 34426522)
Mayo Clinic Laboratories, Mayo Clinic RCV001549598 SCV004226603 pathogenic not provided 2023-03-28 criteria provided, single submitter clinical testing PP3, PP4, PM2, PM3, PM5, PS3
Natera, Inc. RCV001831618 SCV002085253 pathogenic Galactosemia 2017-03-17 no assertion criteria provided clinical testing

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