rs1051519
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_005327.7(HADH):c.456G>T(p.Gln152His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,613,826 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005327.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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HADH | NM_005327.7 | c.456G>T | p.Gln152His | missense_variant | Exon 4 of 8 | ENST00000309522.8 | NP_005318.6 | |
HADH | NM_001184705.4 | c.456G>T | p.Gln152His | missense_variant | Exon 4 of 9 | NP_001171634.3 | ||
HADH | NM_001331027.2 | c.468G>T | p.Gln156His | missense_variant | Exon 4 of 8 | NP_001317956.2 | ||
HADH | XR_007096395.1 | n.500G>T | non_coding_transcript_exon_variant | Exon 4 of 8 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00187 AC: 284AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00180 AC: 452AN: 251480Hom.: 0 AF XY: 0.00175 AC XY: 238AN XY: 135914
GnomAD4 exome AF: 0.00259 AC: 3788AN: 1461544Hom.: 3 Cov.: 31 AF XY: 0.00249 AC XY: 1807AN XY: 727074
GnomAD4 genome AF: 0.00186 AC: 284AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.00167 AC XY: 124AN XY: 74458
ClinVar
Submissions by phenotype
not provided Benign:3
HADH: BP4, BS1 -
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This variant is associated with the following publications: (PMID: 8687463) -
Deficiency of 3-hydroxyacyl-CoA dehydrogenase Uncertain:1Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
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not specified Uncertain:1
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Deficiency of 3-hydroxyacyl-CoA dehydrogenase;C1864948:Hyperinsulinemic hypoglycemia, familial, 4 Uncertain:1
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Monogenic diabetes Uncertain:1
ACMG Criteria:PP3 (3 predictors), BP4 (7 predictors) -
Hyperinsulinemic hypoglycemia, familial, 4 Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
HADH-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at