chr12-120997550-C-T
Variant summary
Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000545.8(HNF1A):c.1386C>T(p.Val462Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,613,532 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 Likely benign (★★).
Frequency
Consequence
NM_000545.8 synonymous
Scores
Clinical Significance
Conservation
Publications
- monogenic diabetesInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- type 1 diabetes mellitus 20Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp
- diabetes mellitus, noninsulin-dependentInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- maturity-onset diabetes of the young type 3Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
- hyperinsulinism due to HNF1A deficiencyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- maturity-onset diabetes of the youngInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- nonpapillary renal cell carcinomaInheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Benign. The variant received -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.1386C>T | p.Val462Val | synonymous_variant | Exon 7 of 10 | ENST00000257555.11 | NP_000536.6 | |
HNF1A | NM_001306179.2 | c.1386C>T | p.Val462Val | synonymous_variant | Exon 7 of 10 | NP_001293108.2 | ||
HNF1A | XM_024449168.2 | c.1386C>T | p.Val462Val | synonymous_variant | Exon 7 of 9 | XP_024304936.1 | ||
HNF1A | NM_001406915.1 | c.1309+808C>T | intron_variant | Intron 6 of 8 | NP_001393844.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.1386C>T | p.Val462Val | synonymous_variant | Exon 7 of 10 | 1 | NM_000545.8 | ENSP00000257555.5 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152174Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.000176 AC: 44AN: 249718 AF XY: 0.000140 show subpopulations
GnomAD4 exome AF: 0.000244 AC: 357AN: 1461240Hom.: 0 Cov.: 38 AF XY: 0.000226 AC XY: 164AN XY: 726984 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000236 AC: 36AN: 152292Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74486 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Benign:2
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Maturity onset diabetes mellitus in young Benign:2
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
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 rs143015301 with MODY3. -
not provided Benign:2
HNF1A: BP4, BP7 -
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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 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at