chrX-153743248-C-T

Variant names:

• chrX-153743248-C-T
• rs1557055319
• NM_000033.4:c.1893C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000033.4(ABCD1):​c.1893C>T​(p.Cys631Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 1,094,837 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000064 (0 hom. 4 hem.)
• Consequence: ABCD1 NM_000033.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: -0.327
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant X-153743248-C-T is Benign according to our data. Variant chrX-153743248-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 528347.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 7 XL,AD gene.

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.1893C>T	p.Cys631Cys	synonymous	Exon 9 of 10	NP_000024.2
	ABCD1	NM_001440747.1		c.2193C>T	p.Cys731Cys	synonymous	Exon 10 of 11	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-4670G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.1893C>T	p.Cys631Cys	synonymous	Exon 9 of 10	ENSP00000218104.3	P33897
	ABCD1	ENST00000862307.1		c.2193C>T	p.Cys731Cys	synonymous	Exon 10 of 11	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.2163C>T	p.Cys721Cys	synonymous	Exon 10 of 11	ENSP00000532365.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.00000570 AC: 1 AN: 175484 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000371

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 AF: 0.00000639 AC: 7 AN: 1094837 Hom.: 0 Cov.: 32 AF XY: 0.0000111 AC XY: 4 AN XY: 361463

African (AFR) AF: 0.00 AC: 0 AN: 26333

American (AMR) AF: 0.000171 AC: 6 AN: 35039

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19323

East Asian (EAS) AF: 0.00 AC: 0 AN: 30165

South Asian (SAS) AF: 0.00 AC: 0 AN: 53586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3035

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841273

Other (OTH) AF: 0.00 AC: 0 AN: 45909

GnomAD4 genome Cov.: 25

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	1	Adrenoleukodystrophy (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.6
DANN	Benign	0.90
PhyloP100		-0.33

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

Other links and lift over

dbSNP: rs1557055319; hg19: chrX-153008702;