Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000022051 | SCV000919402 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2023-11-14 | criteria provided, single submitter | clinical testing | Variant summary: GALT c.98G>A (p.Arg33His) results in a non-conservative amino acid change located in the Galactose-1-phosphate uridyl transferase, N-terminal domain 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 251524 control chromosomes (gnomAD). c.98G>A has been reported in the literature in multiple individuals affected with Galactosemia (examples: Gort_2006, Garcia_2016, Tele Kisa_2019). These data indicate that the variant is very likely to be associated with disease. At least one publication reports GALT enzyme activities below the normal range in erythrocytes from patients, suggesting a deleterious effect of the variant (Gort_2006 and Garcia_2016). The following publications have been ascertained in the context of this evaluation (PMID: 20008339, 27176039, 17041746, 27005423, 31194682). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV000022051 | SCV002284931 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2022-03-22 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Arg33 amino acid residue in GALT. Other variant(s) that disrupt this residue have been observed in individuals with GALT-related conditions (PMID: 25592817, 31194895), which suggests that this may be a clinically significant amino acid residue. 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: 25124). This missense change has been observed in individual(s) with galactosemia (PMID: 17041746). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 33 of the GALT protein (p.Arg33His). |
| Baylor Genetics | RCV000022051 | SCV005058873 | likely pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2023-12-10 | criteria provided, single submitter | clinical testing |