chr12-120978920-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 4P and 3B. PM1PM2BP4_ModerateBP6
The NM_000545.8(HNF1A):c.152G>A(p.Gly51Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,611,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G51V) has been classified as Uncertain significance.
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 | UniProt |
---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.152G>A | p.Gly51Asp | missense_variant | 1/10 | ENST00000257555.11 | |
HNF1A | NM_001306179.2 | c.152G>A | p.Gly51Asp | missense_variant | 1/10 | ||
HNF1A | NM_001406915.1 | c.152G>A | p.Gly51Asp | missense_variant | 1/9 | ||
HNF1A | XM_024449168.2 | c.152G>A | p.Gly51Asp | missense_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.152G>A | p.Gly51Asp | missense_variant | 1/10 | 1 | NM_000545.8 | P4 | |
HNF1A-AS1 | ENST00000619441.1 | n.128+1724C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000834 AC: 2AN: 239690Hom.: 0 AF XY: 0.00000763 AC XY: 1AN XY: 130976
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459452Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2AN XY: 725982
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HNF1A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 1727231). This variant has not been reported in the literature in individuals affected with HNF1A-related conditions. This variant is present in population databases (rs776710848, gnomAD 0.002%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 51 of the HNF1A protein (p.Gly51Asp). - |
Maturity onset diabetes mellitus in young Benign:1
Likely benign, 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 rs776710848 with MODY3. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at