chrX-153725282-AGGCCCC-CT

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_000033.4(ABCD1):​c.16_22delinsCT​(p.Arg6LeufsTer187) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 25)

Consequence

ABCD1
NM_000033.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.53
Variant links:
Genes affected
ABCD1 (HGNC:61): (ATP binding cassette subfamily D member 1) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ALD subfamily, which is involved in peroxisomal import of fatty acids and/or fatty acyl-CoAs in the organelle. All known peroxisomal ABC transporters are half transporters which require a partner half transporter molecule to form a functional homodimeric or heterodimeric transporter. This peroxisomal membrane protein is likely involved in the peroxisomal transport or catabolism of very long chain fatty acids. Defects in this gene have been identified as the underlying cause of adrenoleukodystrophy, an X-chromosome recessively inherited demyelinating disorder of the nervous system. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 71 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-153725282-AGGCCCC-CT is Pathogenic according to our data. Variant chrX-153725282-AGGCCCC-CT is described in ClinVar as [Pathogenic]. Clinvar id is 528340.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCD1NM_000033.4 linkuse as main transcriptc.16_22delinsCT p.Arg6LeufsTer187 frameshift_variant 1/10 ENST00000218104.6 NP_000024.2
ABCD1XM_047441916.1 linkuse as main transcriptc.16_22delinsCT p.Arg6LeufsTer187 frameshift_variant 1/11 XP_047297872.1
ABCD1XM_047441917.1 linkuse as main transcriptc.16_22delinsCT p.Arg6LeufsTer187 frameshift_variant 1/8 XP_047297873.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCD1ENST00000218104.6 linkuse as main transcriptc.16_22delinsCT p.Arg6LeufsTer187 frameshift_variant 1/101 NM_000033.4 ENSP00000218104 P1

Frequencies

GnomAD3 genomes
Cov.:
25
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
25

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Adrenoleukodystrophy Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 11, 2017While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ABCD1 are known to be pathogenic (PMID: 11748843). This variant has not been reported in the literature in individuals with ABCD1-related disease. This sequence change creates a premature translational stop signal (p.Arg6Leufs*187) in the ABCD1 gene. It is expected to result in an absent or disrupted protein product. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs1557052133; hg19: chrX-152990737; API