12-120978511-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000433033.3(HNF1A-AS1):n.134+1103T>C variant causes a intron change. The variant allele was found at a frequency of 0.000153 in 561,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★★).
Frequency
Consequence
ENST00000433033.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.-258A>G | upstream_gene_variant | ENST00000257555.11 | NP_000536.6 | |||
HNF1A | NM_001306179.2 | c.-258A>G | upstream_gene_variant | NP_001293108.2 | ||||
HNF1A | NM_001406915.1 | c.-258A>G | upstream_gene_variant | NP_001393844.1 | ||||
HNF1A | XM_024449168.2 | c.-258A>G | upstream_gene_variant | XP_024304936.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.-258A>G | upstream_gene_variant | 1 | NM_000545.8 | ENSP00000257555.5 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152024Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.000154 AC: 63AN: 409416Hom.: 0 Cov.: 0 AF XY: 0.000111 AC XY: 24AN XY: 216918
GnomAD4 genome AF: 0.000151 AC: 23AN: 152024Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74262
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
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Diabetes mellitus type 1;C0011860:Type 2 diabetes mellitus;C1838100:Maturity-onset diabetes of the young type 3;C1840646:Hepatic adenomas, familial;C2675866:Type 1 diabetes mellitus 20;CN074294:Nonpapillary renal cell carcinoma Uncertain:1
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Monogenic diabetes Uncertain:1
The c.-258A>G variant in the HNF1 homeobox A gene, HNF1A, is located in the promoter of NM_000545.8. This variant is located in the promoter of NM_000545.8. This variant is located at the HNF1A binding site (c.-238 to c.-259) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). Additionally, this variant was identified in an individual with a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A) (PP4; internal lab contributor). In summary, c.-258A>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 2.1.0, approved 8/11/2023): PM1_Supporting, PP4. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at