rs199723613

Variant names:

• chrX-153743269-C-T
• rs199723613
• NM_000033.4:c.1914C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_000033.4(ABCD1):​c.1914C>T​(p.Asp638Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000978 in 1,206,150 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000062 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.00010 (0 hom. 39 hem.)
• Consequence: ABCD1 NM_000033.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:4
• Conservation: PhyloP100: -0.429
• 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=-0.51).
• BP6: Variant X-153743269-C-T is Benign according to our data. Variant chrX-153743269-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 528350.
• BP7: Synonymous conserved (PhyloP=-0.429 with no splicing effect.
• BS2: High AC in GnomAd4 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.1914C>T	p.Asp638Asp	synonymous	Exon 9 of 10	NP_000024.2
	ABCD1	NM_001440747.1		c.2214C>T	p.Asp738Asp	synonymous	Exon 10 of 11	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-4691G>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.1914C>T	p.Asp638Asp	synonymous	Exon 9 of 10	ENSP00000218104.3	P33897
	ABCD1	ENST00000862307.1		c.2214C>T	p.Asp738Asp	synonymous	Exon 10 of 11	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.2184C>T	p.Asp728Asp	synonymous	Exon 10 of 11	ENSP00000532365.1

Frequencies

GnomAD3 genomes AF: 0.0000621 AC: 7 AN: 112749 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000638 AC: 11 AN: 172412 AF XY: 0.0000507

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: 0.000132

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000102 AC: 111 AN: 1093401 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 39 AN XY: 360159

African (AFR) AF: 0.00 AC: 0 AN: 26316

American (AMR) AF: 0.00 AC: 0 AN: 34873

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19284

East Asian (EAS) AF: 0.00 AC: 0 AN: 30099

South Asian (SAS) AF: 0.0000188 AC: 1 AN: 53315

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40080

Middle Eastern (MID) AF: 0.000329 AC: 1 AN: 3037

European-Non Finnish (NFE) AF: 0.000120 AC: 101 AN: 840519

Other (OTH) AF: 0.000174 AC: 8 AN: 45878

GnomAD4 genome AF: 0.0000621 AC: 7 AN: 112749 Hom.: 0 Cov.: 24 AF XY: 0.0000573 AC XY: 2 AN XY: 34905

African (AFR) AF: 0.0000322 AC: 1 AN: 31025

American (AMR) AF: 0.00 AC: 0 AN: 10788

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2660

East Asian (EAS) AF: 0.00 AC: 0 AN: 3562

South Asian (SAS) AF: 0.00 AC: 0 AN: 2771

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6263

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53233

Other (OTH) AF: 0.00 AC: 0 AN: 1521

Alfa AF: 0.000654 Hom.: 1

Bravo AF: 0.0000680

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	2	Adrenoleukodystrophy (3)
-	-	1	ABCD1-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	2.1
DANN	Benign	0.93
PhyloP100		-0.43
Mutation Taster		=99/1	polymorphism

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: rs199723613; hg19: chrX-153008723; COSMIC: COSV54385996; COSMIC: COSV54385996;