ClinVar Miner

Submissions for variant NM_024642.5(GALNT12):c.303C>G (p.His101Gln)

gnomAD frequency: 0.00021  dbSNP: rs201926457
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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 RCV000473689 SCV000551396 uncertain significance not provided 2024-10-30 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 101 of the GALNT12 protein (p.His101Gln). This variant is present in population databases (rs201926457, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with colorectal cancer (PMID: 29749045, 33193653). ClinVar contains an entry for this variant (Variation ID: 410580). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt GALNT12 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects GALNT12 function (PMID: 29749045). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004022792 SCV000673543 likely benign not specified 2020-06-24 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV003401483 SCV004120351 uncertain significance GALNT12-related disorder 2023-03-10 criteria provided, single submitter clinical testing The GALNT12 c.303C>G variant is predicted to result in the amino acid substitution p.His101Gln. This variant was reported in two colorectal cancer cohort studies (Evans et al. 2018. PubMed ID: 29749045; Djursby et al. 2020. PubMed ID: 33193653). The p.His101Gln change was reported to result in reduced enzyme activity in an in vitro assay (Evans et al. 2018. PubMed ID: 29749045). This variant is reported in 0.035% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-101570283-C-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000473689 SCV004219777 benign not provided 2022-11-23 criteria provided, single submitter clinical testing

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