rs137852769
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000182.5(HADHA):c.1528G>T(p.Glu510Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000182.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HADHA | NM_000182.5 | c.1528G>T | p.Glu510Ter | stop_gained | 15/20 | ENST00000380649.8 | |
GAREM2 | XM_011532567.4 | c.1684-7049C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HADHA | ENST00000380649.8 | c.1528G>T | p.Glu510Ter | stop_gained | 15/20 | 1 | NM_000182.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152014Hom.: 0 Cov.: 30
GnomAD4 exome Cov.: 30
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152014Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74242
ClinVar
Submissions by phenotype
HADHA-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 05, 2024 | The HADHA c.1528G>T variant is predicted to result in premature protein termination (p.Glu510*). To our knowledge, this variant has not been previously reported in the literature in association with disease. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in HADHA are expected to be pathogenic. This variant is interpreted as likely pathogenic. - |
Mitochondrial trifunctional protein deficiency;C3711645:Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 16, 2020 | This sequence change creates a premature translational stop signal (p.Glu510*) in the HADHA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with HADHA-related conditions. Loss-of-function variants in HADHA are known to be pathogenic (PMID: 7738175, 21103935, 21549624, 22459206). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at