4-107989926-CCA-C
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PVS1PM2BP6
The ENST00000505878.4(HADH):c.175_176delAC(p.Thr59HisfsTer71) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000505878.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HADH | NM_005327.7 | c.-3_-2delAC | 5_prime_UTR_variant | Exon 1 of 8 | ENST00000309522.8 | NP_005318.6 | ||
HADH | NM_001184705.4 | c.-3_-2delAC | 5_prime_UTR_variant | Exon 1 of 9 | NP_001171634.3 | |||
HADH | XR_007096395.1 | n.42_43delAC | non_coding_transcript_exon_variant | Exon 1 of 8 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000452 AC: 11AN: 243394Hom.: 0 AF XY: 0.0000528 AC XY: 7AN XY: 132472
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1459700Hom.: 0 AF XY: 0.0000179 AC XY: 13AN XY: 726094
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152372Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74512
ClinVar
Submissions by phenotype
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