rs118204093
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004035.7(ACOX1):c.442C>T(p.Arg148*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000274 in 1,461,578 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_004035.7 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461578Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727128
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Acyl-CoA oxidase deficiency;C5394554:Mitchell syndrome Pathogenic:1
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Acyl-CoA oxidase deficiency Pathogenic:1
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not provided Pathogenic:1
The R148X nonsense variant in the ACOX1 gene has been reported previously in association with peroxisomal acyl-CoA oxidase deficiency in an individual who was homozygous for R148X (Ferdinandusse et al., 2007). The R148X variant is not observed in large population cohorts (Lek et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret R148X to be a pathogenic variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at