Variant rs797045080 details in Genebe, Genetics Data Aggregator

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

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: -0.966

Variant links:

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]

ACOX1 links:

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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 linkuse as main transcript	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 linkuse as main transcript	c.1851del	p.Gly618AlafsTer24	frameshift_variant	13/14	1	NM_004035.7	A1	Q15067-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251484

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.26

Position offset: 12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over