rs587778394
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2_SupportingPM1_Supporting
This summary comes from the ClinGen Evidence Repository: The c.73G>A variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of Alanine to Threonine at codon 25 (p.(Ala25Thr)) of transcript NM_000545.8. This variant is located within the dimerization domain (codons 1-32) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.73G>A meets the criteria to be classified as uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/2021): PM1_supporting, PM2_supporting. LINK:https://erepo.genome.network/evrepo/ui/classification/CA160004/MONDO:0015967/017
Frequency
Consequence
NM_000545.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.73G>A | p.Ala25Thr | missense_variant | 1/10 | ENST00000257555.11 | |
HNF1A | NM_001306179.2 | c.73G>A | p.Ala25Thr | missense_variant | 1/10 | ||
HNF1A | NM_001406915.1 | c.73G>A | p.Ala25Thr | missense_variant | 1/9 | ||
HNF1A | XM_024449168.2 | c.73G>A | p.Ala25Thr | missense_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.73G>A | p.Ala25Thr | missense_variant | 1/10 | 1 | NM_000545.8 | P4 | |
HNF1A-AS1 | ENST00000619441.1 | n.128+1803C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461076Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0AN XY: 726868
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Monogenic diabetes Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Monogenic Diabetes Variant Curation Expert Panel | Apr 01, 2022 | The c.73G>A variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of Alanine to Threonine at codon 25 (p.(Ala25Thr)) of transcript NM_000545.8. This variant is located within the dimerization domain (codons 1-32) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.73G>A meets the criteria to be classified as uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/2021): PM1_supporting, PM2_supporting. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Maturity onset diabetes mellitus in young Other:1
Uncertain risk allele, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | 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 rs587778394 with MODY3. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at