ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.140G>A (p.Gly47Glu)

gnomAD frequency: 0.00001  dbSNP: rs1391743259
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Monogenic Diabetes Variant Curation Expert Panel RCV002222081 SCV002499474 uncertain significance Monogenic diabetes 2022-04-02 reviewed by expert panel curation The c.140G>A variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of glycine to glutamate at codon 47 (p.(Gly47Glu)) of NM_000545.8. Functional studies demonstrated the p.Gly47Arg protein has normal nuclear localization and transactivation above 75% of wildtype, indicating that this variant does not impact protein function (PMID: 12574234) (BS3_Supporting). Additionally, this variant is absent from gnomAD v2.1.1 (PM2_Supporting). Another missense variant, c.139G>C (p.(Gly47Arg)), has been classified as a VUS by the ClinGen MDEP; therefore, PM5 will not be applied. This variant was identified in an individual with diabetes; however, the calculated MODY probability is <50%, and PP4 cannot be applied (PMID: 12574234, internal lab contributor). In summary, c.140G>A meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.0, approved 9/30/21): BS3_Supporting, PM2_supporting
Fulgent Genetics, Fulgent Genetics RCV002481029 SCV002780561 uncertain significance Diabetes mellitus type 1; Type 1 diabetes mellitus 20; Maturity-onset diabetes of the young type 3; Type 2 diabetes mellitus; Hepatic adenomas, familial; Nonpapillary renal cell carcinoma 2022-02-04 criteria provided, single submitter clinical testing

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