rs797045080
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_ModeratePP5_ModerateBS2
The NM_004035.7(ACOX1):c.1851del(p.Gly618AlafsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
ACOX1
NM_004035.7 frameshift
NM_004035.7 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.966
Genes affected
ACOX1 (HGNC:119): (acyl-CoA oxidase 1) The protein encoded by this gene is the first enzyme of the fatty acid beta-oxidation pathway, which catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs. It donates electrons directly to molecular oxygen, thereby producing hydrogen peroxide. Defects in this gene result in pseudoneonatal adrenoleukodystrophy, a disease that is characterized by accumulation of very long chain fatty acids. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0666 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PP5
?
Variant 17-75948334-CA-C is Pathogenic according to our data. Variant chr17-75948334-CA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 208560.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAdExome4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACOX1 | NM_004035.7 | c.1851del | p.Gly618AlafsTer24 | frameshift_variant | 13/14 | ENST00000293217.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACOX1 | ENST00000293217.10 | c.1851del | p.Gly618AlafsTer24 | frameshift_variant | 13/14 | 1 | NM_004035.7 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251484Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135912
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727240
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GnomAD4 genome ? Cov.: 31
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Acyl-CoA oxidase deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 31, 2014 | The c.1851delT variant in ACOX1 has not been reported in individuals with peroxisomal acyl-CoA oxidase deficiency or in large population studies. This frameshift variant is predicted to alter the protein’s amino acid sequence beginning at position 618 and lead to a premature termination codon 24 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In summary, this variant is likely pathogenic, though additional studies are required to fully establish its clinical significance. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 12
Find out detailed SpliceAI scores and Pangolin per-transcript scores at