12-120994314-GC-GCCC
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_000545.8(HNF1A):c.871_872dupCC(p.Gly292GlnfsTer51) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,550 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
HNF1A
NM_000545.8 frameshift
NM_000545.8 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.88
Genes affected
HNF1A (HGNC:11621): (HNF1 homeobox A) The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.871_872dupCC | p.Gly292GlnfsTer51 | frameshift_variant | Exon 4 of 10 | ENST00000257555.11 | NP_000536.6 | |
HNF1A | NM_001306179.2 | c.871_872dupCC | p.Gly292GlnfsTer51 | frameshift_variant | Exon 4 of 10 | NP_001293108.2 | ||
HNF1A | NM_001406915.1 | c.871_872dupCC | p.Gly292GlnfsTer51 | frameshift_variant | Exon 4 of 9 | NP_001393844.1 | ||
HNF1A | XM_024449168.2 | c.871_872dupCC | p.Gly292GlnfsTer51 | frameshift_variant | Exon 4 of 9 | XP_024304936.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.871_872dupCC | p.Gly292GlnfsTer51 | frameshift_variant | Exon 4 of 10 | 1 | NM_000545.8 | ENSP00000257555.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1453550Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 722642
GnomAD4 exome
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1
AN:
1453550
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Cov.:
35
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1
AN XY:
722642
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
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Name
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at