rs1557055392

Variant names:

• chrX-153743494-A-ACG
• rs1557055392
• NM_000033.4:c.1998_1999insGC

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000033.4(ABCD1):​c.1998_1999insGC​(p.His667AlafsTer25) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ABCD1 NM_000033.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.04
• Publications: 0 publications found

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]

PLXNB3-AS1 (HGNC:40454): (PLXNB3 antisense RNA 1)

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 20 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-153743494-A-ACG is Pathogenic according to our data. Variant chrX-153743494-A-ACG is described in ClinVar as Pathogenic. ClinVar VariationId is 458638.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000033.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	NM_000033.4	MANE Select	c.1998_1999insGC	p.His667AlafsTer25	frameshift	Exon 10 of 10	NP_000024.2
	ABCD1	NM_001440747.1		c.2298_2299insGC	p.His767AlafsTer25	frameshift	Exon 11 of 11	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-4917_90-4916insCG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.1998_1999insGC	p.His667AlafsTer25	frameshift	Exon 10 of 10	ENSP00000218104.3	P33897
	ABCD1	ENST00000862307.1		c.2298_2299insGC	p.His767AlafsTer25	frameshift	Exon 11 of 11	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.2268_2269insGC	p.His757AlafsTer25	frameshift	Exon 11 of 11	ENSP00000532365.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Adrenoleukodystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.0

Splicing

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

Other links and lift over

dbSNP: rs1557055392; hg19: chrX-153008948;