NM_000033.4:c.1533C>T

Variant names:

• chrX-153740136-C-T
• rs782370364
• NM_000033.4:c.1533C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP6_Moderate BP7 BS2

The NM_000033.4(ABCD1):​c.1533C>T​(p.Cys511Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,209,290 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.000022 (0 hom. 5 hem.)
• Consequence: ABCD1 NM_000033.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0960
• Publications: 1 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 -7 ACMG points.

• BP6: Variant X-153740136-C-T is Benign according to our data. Variant chrX-153740136-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1093692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.096 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 24 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.1533C>T	p.Cys511Cys	synonymous	Exon 6 of 10	NP_000024.2
	ABCD1	NM_001440747.1		c.1833C>T	p.Cys611Cys	synonymous	Exon 7 of 11	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-1558G>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.1533C>T	p.Cys511Cys	synonymous	Exon 6 of 10	ENSP00000218104.3	P33897
	ABCD1	ENST00000862307.1		c.1833C>T	p.Cys611Cys	synonymous	Exon 7 of 11	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.1803C>T	p.Cys601Cys	synonymous	Exon 7 of 11	ENSP00000532365.1

Frequencies

GnomAD3 genomes AF: 0.0000354 AC: 4 AN: 112908 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000275 AC: 5 AN: 182133 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000407

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000246

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 24 AN: 1096382 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 5 AN XY: 361910

African (AFR) AF: 0.00 AC: 0 AN: 26377

American (AMR) AF: 0.00 AC: 0 AN: 35103

Ashkenazi Jewish (ASJ) AF: 0.000931 AC: 18 AN: 19329

East Asian (EAS) AF: 0.00 AC: 0 AN: 30158

South Asian (SAS) AF: 0.00 AC: 0 AN: 53974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40395

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 840910

Other (OTH) AF: 0.000109 AC: 5 AN: 46004

GnomAD4 genome AF: 0.0000354 AC: 4 AN: 112908 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 35076

African (AFR) AF: 0.00 AC: 0 AN: 31100

American (AMR) AF: 0.00 AC: 0 AN: 10781

Ashkenazi Jewish (ASJ) AF: 0.00150 AC: 4 AN: 2658

East Asian (EAS) AF: 0.00 AC: 0 AN: 3594

South Asian (SAS) AF: 0.00 AC: 0 AN: 2786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53256

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Adrenoleukodystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.16
DANN	Benign	0.85
PhyloP100		-0.096
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs782370364; hg19: chrX-153005590;