rs375654005
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PP3_ModeratePP5_Very_Strong
The NM_000183.3(HADHB):c.686G>A(p.Arg229Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,650 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R229L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000183.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HADHB | NM_000183.3 | c.686G>A | p.Arg229Gln | missense_variant | 9/16 | ENST00000317799.10 | |
HADHB | NM_001281512.2 | c.641G>A | p.Arg214Gln | missense_variant | 8/15 | ||
HADHB | NM_001281513.2 | c.620G>A | p.Arg207Gln | missense_variant | 10/17 | ||
HADHB | XM_011532803.2 | c.686G>A | p.Arg229Gln | missense_variant | 9/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HADHB | ENST00000317799.10 | c.686G>A | p.Arg229Gln | missense_variant | 9/16 | 1 | NM_000183.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251326Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135832
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461650Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727144
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 02, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30990523) - |
Mitochondrial trifunctional protein deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 15, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at