4-108014460-G-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_005327.7(HADH):c.291G>T(p.Leu97Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,614,098 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005327.7 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HADH | NM_005327.7 | c.291G>T | p.Leu97Leu | synonymous_variant | Exon 3 of 8 | ENST00000309522.8 | NP_005318.6 | |
HADH | NM_001184705.4 | c.291G>T | p.Leu97Leu | synonymous_variant | Exon 3 of 9 | NP_001171634.3 | ||
HADH | NM_001331027.2 | c.303G>T | p.Leu101Leu | synonymous_variant | Exon 3 of 8 | NP_001317956.2 | ||
HADH | XR_007096395.1 | n.335G>T | non_coding_transcript_exon_variant | Exon 3 of 8 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000350 AC: 88AN: 251490Hom.: 1 AF XY: 0.000515 AC XY: 70AN XY: 135920
GnomAD4 exome AF: 0.000150 AC: 220AN: 1461880Hom.: 2 Cov.: 32 AF XY: 0.000210 AC XY: 153AN XY: 727242
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74446
ClinVar
Submissions by phenotype
Deficiency of 3-hydroxyacyl-CoA dehydrogenase Uncertain:1Benign:1
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Hyperinsulinism, Dominant/Recessive Uncertain:1
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Hyperinsulinemic hypoglycemia Benign: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 rs552317372 in congenital hyperinsulinism is yet to be ascertained. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at