ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.326+4A>G

dbSNP: rs193922595
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Monogenic Diabetes Variant Curation Expert Panel RCV002222006 SCV002499494 uncertain significance Monogenic diabetes 2022-04-07 reviewed by expert panel curation The computational splicing predictor SpliceAI gives a score of 0.56 for donor loss, predicting that the c.326+4A>G variant in the HNF1 homeobox A gene, HNF1A (NM_000545.8), variant disrupts the donor site of intron 1 of HNF1A (PP3). This variant was also identified in an individual with a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A, and negative antibodies) (PP4_Moderate; PMID: 28862987). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in three unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (PMID: 28862987, internal lab contributors). In summary, c.326+4A>G 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 1.1, approved 9/30/2021): PP3, PP4_Moderate, PM2_Supporting.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030500 SCV000053171 uncertain Maturity-onset diabetes of the young type 3 2011-08-18 criteria provided, single submitter curation Converted during submission to Uncertain significance.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002326708 SCV002601687 likely risk allele Maturity onset diabetes mellitus in young criteria provided, single submitter research Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs193922595 with MODY3.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.