X-153743540-C-T

Variant names:

• chrX-153743540-C-T
• rs782327280
• NM_000033.4:c.2043C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_000033.4(ABCD1):​c.2043C>T​(p.Phe681Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000306 in 1,201,573 control chromosomes in the GnomAD database, including 1 homozygotes. There are 128 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., 11 hem., cov: 24)
  • Exomes 𝑓: 0.00031 (1 hom. 117 hem.)
• Consequence: ABCD1 NM_000033.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.27
• 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant X-153743540-C-T is Benign according to our data. Variant chrX-153743540-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 528352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.27 with no splicing effect.
• BS2: High AC in GnomAd4 at 29 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.2043C>T	p.Phe681Phe	synonymous	Exon 10 of 10	NP_000024.2
	ABCD1	NM_001440747.1		c.2343C>T	p.Phe781Phe	synonymous	Exon 11 of 11	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-4962G>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.2043C>T	p.Phe681Phe	synonymous	Exon 10 of 10	ENSP00000218104.3
	ABCD1	ENST00000862307.1		c.2343C>T	p.Phe781Phe	synonymous	Exon 11 of 11	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.2313C>T	p.Phe771Phe	synonymous	Exon 11 of 11	ENSP00000532365.1

Frequencies

GnomAD3 genomes AF: 0.000257 AC: 29 AN: 112687 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: 0.000356

Gnomad FIN AF: 0.000160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000489

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000360 AC: 59 AN: 163919 AF XY: 0.000428

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000423

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000338

Gnomad NFE exome AF: 0.000648

Gnomad OTH exome AF: 0.000243

GnomAD4 exome AF: 0.000311 AC: 339 AN: 1088886 Hom.: 1 Cov.: 37 AF XY: 0.000328 AC XY: 117 AN XY: 356638

African (AFR) AF: 0.0000381 AC: 1 AN: 26247

American (AMR) AF: 0.00 AC: 0 AN: 34455

Ashkenazi Jewish (ASJ) AF: 0.000521 AC: 10 AN: 19206

East Asian (EAS) AF: 0.00 AC: 0 AN: 29929

South Asian (SAS) AF: 0.000303 AC: 16 AN: 52810

European-Finnish (FIN) AF: 0.000352 AC: 14 AN: 39720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2881

European-Non Finnish (NFE) AF: 0.000333 AC: 279 AN: 837963

Other (OTH) AF: 0.000416 AC: 19 AN: 45675

GnomAD4 genome AF: 0.000257 AC: 29 AN: 112687 Hom.: 0 Cov.: 24 AF XY: 0.000316 AC XY: 11 AN XY: 34861

African (AFR) AF: 0.0000322 AC: 1 AN: 31069

American (AMR) AF: 0.00 AC: 0 AN: 10737

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3558

South Asian (SAS) AF: 0.000356 AC: 1 AN: 2807

European-Finnish (FIN) AF: 0.000160 AC: 1 AN: 6243

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000489 AC: 26 AN: 53193

Other (OTH) AF: 0.00 AC: 0 AN: 1504

Alfa AF: 0.000434 Hom.: 3

Bravo AF: 0.000306

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Adrenoleukodystrophy (3)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	2.4
DANN	Benign	0.90
PhyloP100		-1.3
Mutation Taster		=98/2	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: rs782327280; hg19: chrX-153008994;