ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.413C>T (p.Thr138Met)

gnomAD frequency: 0.00003  dbSNP: rs111033686
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Myriad Genetics, Inc. RCV000022107 SCV001193822 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2019-12-19 criteria provided, single submitter clinical testing NM_000155.3(GALT):c.413C>T(T138M) is classified as likely pathogenic in the context of galactosemia. Sources cited for classification include the following: PMID 8741038, 17876724, 10960497, 22944367 and 11754113. Classification of NM_000155.3(GALT):c.413C>T(T138M) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses and is very rare or not present in genetic databases of healthy individuals. Please note: this variant was assessed in the context of healthy population screening.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000022107 SCV001363670 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2020-09-28 criteria provided, single submitter clinical testing Variant summary: GALT c.413C>T (p.Thr138Met) 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 allele was found at a frequency of 1.2e-05 in 251494 control chromosomes. c.413C>T has been reported in the literature in individuals affected with Galactosemia (examples- Elsas_1995, Shin_1999, Yang_2002, Calderon_2007, Boutron_2012). These data indicate that the variant is likely to be associated with disease. Several publications report experimental evidence evaluating an impact on protein function. At least two studies report that the variant retains less than 10% of the normal GALT enzymatic activity (examples- Shin_1999, Berry_2000). Two other ClinVar submitters (evaluation after 2014) have cited the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000022107 SCV001386289 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2023-12-28 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 138 of the GALT protein (p.Thr138Met). This variant is present in population databases (rs111033686, gnomAD 0.006%). This missense change has been observed in individual(s) with galactosemia (PMID: 7887416, 8741038, 11397328, 11754113, 22743281, 22944367). ClinVar contains an entry for this variant (Variation ID: 25174). 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 80%. For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV001507744 SCV001713483 pathogenic not provided 2021-03-23 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000022107 SCV002813904 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2022-02-25 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000022107 SCV003825783 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2022-01-17 criteria provided, single submitter clinical testing
Baylor Genetics RCV000022107 SCV004198499 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2023-10-18 criteria provided, single submitter clinical testing
Natera, Inc. RCV001831597 SCV002085202 pathogenic Galactosemia 2017-03-17 no assertion criteria provided clinical testing

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