4-107989817-CG-C
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The ENST00000505878.4(HADH):βc.63delGβ(p.Arg22AlafsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000965 in 1,191,700 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain risk allele (β β ).
Frequency
Consequence
ENST00000505878.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HADH | ENST00000505878.4 | c.63delG | p.Arg22AlafsTer7 | frameshift_variant | Exon 1 of 9 | 1 | ENSP00000425952.2 | |||
HADH | ENST00000603302 | c.-115delG | 5_prime_UTR_variant | Exon 1 of 9 | 1 | ENSP00000474560.1 | ||||
HADH | ENST00000638621.1 | c.-115delG | upstream_gene_variant | 5 | ENSP00000491581.1 |
Frequencies
GnomAD3 genomes AF: 0.000506 AC: 77AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000750 AC: 7AN: 93356Hom.: 0 AF XY: 0.0000588 AC XY: 3AN XY: 50978
GnomAD4 exome AF: 0.0000375 AC: 39AN: 1039402Hom.: 0 Cov.: 14 AF XY: 0.0000345 AC XY: 18AN XY: 522212
GnomAD4 genome AF: 0.000499 AC: 76AN: 152298Hom.: 0 Cov.: 33 AF XY: 0.000483 AC XY: 36AN XY: 74474
ClinVar
Submissions by phenotype
Deficiency of 3-hydroxyacyl-CoA dehydrogenase;C1864948:Hyperinsulinemic hypoglycemia, familial, 4 Uncertain:1
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Deficiency of 3-hydroxyacyl-CoA dehydrogenase Uncertain:1
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Hyperinsulinism, Dominant/Recessive Uncertain:1
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Hyperinsulinemic hypoglycemia Other:1
Potent mutations in HADH gene are associated with congenital hyperinsulinism, which leads to recurrent hypoglycemia. The condition is exacerbated by stress, fasting or excessive dietary protein. May respond well to diazoxide. However, the role of this particular variant rs537335460 in congenital hyperinsulinism is yet to be ascertained. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at