ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.413C>T (p.Thr138Met) (rs111033686)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Myriad Women's Health, 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 2020-10-13 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 138 of the GALT protein (p.Thr138Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals and families affected with galactosemia (PMID: 11397328, 8741038, 22944367, 11754113, 22743281, 7887416). ClinVar contains an entry for this variant (Variation ID: 25174). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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
Research and Development, ARUP Laboratories RCV000022107 SCV000042784 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2012-12-04 no assertion criteria provided clinical testing Converted during submission to Pathogenic.

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