X-153743257-C-G

Variant names:

• chrX-153743257-C-G
• rs141110958
• NM_000033.4:c.1902C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000033.4(ABCD1):​c.1902C>G​(p.Ala634Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A634A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: ABCD1 NM_000033.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.84
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-4.84 with no splicing effect.

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.1902C>G	p.Ala634Ala	synonymous	Exon 9 of 10	NP_000024.2
	ABCD1	NM_001440747.1		c.2202C>G	p.Ala734Ala	synonymous	Exon 10 of 11	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-4679G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.1902C>G	p.Ala634Ala	synonymous	Exon 9 of 10	ENSP00000218104.3	P33897
	ABCD1	ENST00000862307.1		c.2202C>G	p.Ala734Ala	synonymous	Exon 10 of 11	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.2172C>G	p.Ala724Ala	synonymous	Exon 10 of 11	ENSP00000532365.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000572 AC: 1 AN: 174817 AF XY: 0.0000164

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 3 AN: 1094351 Hom.: 0 Cov.: 32 AF XY: 0.00000554 AC XY: 2 AN XY: 361001

African (AFR) AF: 0.00 AC: 0 AN: 26326

American (AMR) AF: 0.00 AC: 0 AN: 34981

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19317

East Asian (EAS) AF: 0.00 AC: 0 AN: 30128

South Asian (SAS) AF: 0.0000561 AC: 3 AN: 53460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3026

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841059

Other (OTH) AF: 0.00 AC: 0 AN: 45904

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.39
DANN	Benign	0.75
PhyloP100		-4.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs141110958; hg19: chrX-153008711;