20-44355850-T-TA
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_175914.5(HNF4A):c.47dupA(p.Tyr16fs) variant causes a frameshift, stop gained, splice region change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_175914.5 frameshift, stop_gained, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hyperinsulinism due to HNF1A deficiency Pathogenic:1
The duplication of a single nucleotide in the first exon of HNF4A introduces a premature stop codon (p.Tyr16*). This variant is predicted to result in a loss of gene function. This is a novel duplication that has not been reported in the medical literature or in clinical databases. This variant has not been observed in presumably healthy controls in the Genome Aggregation Database. While this variant appears to be novel, a different sequence change that also results in p.Tyr16* (c.48C>G), as well as other nonsense variants in HNF4A, have been described in several individuals with congenital hyperinsulinism (PMID: 20164212, PMID: 17407387, PMID: 23348805 and others). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.