rs1557054859

Positions:

• chrX-153740681-ACGT-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PM4_Supporting

The NM_000033.4(ABCD1):​c.1746_1748del​(p.Val583del) variant causes a inframe deletion 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D581D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 24)
• Consequence: ABCD1 NM_000033.4 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56

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]

LOC124905226 (HGNC:):

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

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a domain ABC transporter (size 226) in uniprot entity ABCD1_HUMAN there are 131 pathogenic changes around while only 17 benign (89%) in NM_000033.4
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000033.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCD1	NM_000033.4	c.1746_1748del	p.Val583del	inframe_deletion	7/10	ENST00000218104.6
LOC124905226	XR_007068350.1	n.864_866del		non_coding_transcript_exon_variant	1/2
ABCD1	XM_047441916.1	c.2046_2048del	p.Val683del	inframe_deletion	8/11
ABCD1	XM_047441917.1	c.*74_*76del		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCD1	ENST00000218104.6	c.1746_1748del	p.Val583del	inframe_deletion	7/10	1	NM_000033.4	P1
PLXNB3-AS1	ENST00000434284.1	n.72-2106_72-2104del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 24

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Adrenoleukodystrophy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital

Nov 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1557054859; hg19: chrX-153006135;