rs202180554
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM2_Supporting
This summary comes from the ClinGen Evidence Repository: The c.225C>A variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of asparagine to glutamate at codon 75 (p.(Asp75Glu)) of NM_000545.8. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with diabetes; however, the calculated MODY probability is <50%; therefore, PP4 could not be applied (internal lab contributors). In summary, c.225C>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 1.1, approved 9/30/21): PM2_Supporting. LINK:https://erepo.genome.network/evrepo/ui/classification/CA386953852/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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.225C>A | p.Asp75Glu | missense_variant | 1/10 | ENST00000257555.11 | NP_000536.6 | |
HNF1A | NM_001306179.2 | c.225C>A | p.Asp75Glu | missense_variant | 1/10 | NP_001293108.2 | ||
HNF1A | NM_001406915.1 | c.225C>A | p.Asp75Glu | missense_variant | 1/9 | NP_001393844.1 | ||
HNF1A | XM_024449168.2 | c.225C>A | p.Asp75Glu | missense_variant | 1/9 | XP_024304936.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.225C>A | p.Asp75Glu | missense_variant | 1/10 | 1 | NM_000545.8 | ENSP00000257555.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000425 AC: 1AN: 235122Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 127988
GnomAD4 exome AF: 0.00000481 AC: 7AN: 1456572Hom.: 0 Cov.: 35 AF XY: 0.00000414 AC XY: 3AN XY: 724152
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 08, 2022 | The c.225C>A variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of asparagine to glutamate at codon 75 (p.(Asp75Glu)) of NM_000545.8. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with diabetes; however, the calculated MODY probability is <50%; therefore, PP4 could not be applied (internal lab contributors). In summary, c.225C>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 1.1, approved 9/30/21): PM2_Supporting. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 04, 2024 | Reported in a patient with MODY in published literature; however, clinical data is not available (PMID: 18003757); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18003757) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at