Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV003228604 | SCV003925187 | uncertain significance | Maturity-onset diabetes of the young type 1; Type 2 diabetes mellitus | 2022-06-17 | criteria provided, single submitter | clinical testing | The c.97G>A p.(Val33Met) variant in the HNF4A gene has not previously been reported in the literature or public variant repositories (ClinVar and LOVD). The c.97G>A variant is observed in 3 alleles (~0.001% minor allele frequency with 0 homozygotes) in population databases (gnomAD v2.1.1 andv3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.97G>A variant in HNF4A is located in exon 1 of this 10-exon gene, and predicted to replace a moderately conserved Valine amino acid with Methionine at position 33 of the encoded protein. In silico predictions are inconclusive of the variant's effect [(CADD v1.6 = 26.3, REVEL = 0.336)]; however, there are no functional studies to support or refute these predictions. Based on available evidence this c.97G>A p.(Val33Met) variant identified in HNF4A is classified as a Variant of Uncertain Significance. |