X-153743667-G-T

Variant names:

• chrX-153743667-G-T
• rs782212963
• NM_000033.4:c.2170G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000033.4(ABCD1):​c.2170G>T​(p.Val724Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000511 in 1,174,419 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V724M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.0000028 (0 hom. 1 hem.)
• Consequence: ABCD1 NM_000033.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07416561).

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.2170G>T	p.Val724Leu	missense	Exon 10 of 10	NP_000024.2
	ABCD1	NM_001440747.1		c.2470G>T	p.Val824Leu	missense	Exon 11 of 11	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-5089C>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.2170G>T	p.Val724Leu	missense	Exon 10 of 10	ENSP00000218104.3	P33897
	ABCD1	ENST00000862307.1		c.2470G>T	p.Val824Leu	missense	Exon 11 of 11	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.2440G>T	p.Val814Leu	missense	Exon 11 of 11	ENSP00000532365.1

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 3 AN: 112104 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000971

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000832 AC: 1 AN: 120251 AF XY: 0.0000259

Gnomad AFR exome AF: 0.000145

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 AF: 0.00000282 AC: 3 AN: 1062315 Hom.: 0 Cov.: 37 AF XY: 0.00000290 AC XY: 1 AN XY: 344679

African (AFR) AF: 0.000118 AC: 3 AN: 25392

American (AMR) AF: 0.00 AC: 0 AN: 30097

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18742

East Asian (EAS) AF: 0.00 AC: 0 AN: 28040

South Asian (SAS) AF: 0.00 AC: 0 AN: 50402

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2864

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 825448

Other (OTH) AF: 0.00 AC: 0 AN: 44634

GnomAD4 genome AF: 0.0000268 AC: 3 AN: 112104 Hom.: 0 Cov.: 24 AF XY: 0.0000292 AC XY: 1 AN XY: 34292

African (AFR) AF: 0.0000971 AC: 3 AN: 30884

American (AMR) AF: 0.00 AC: 0 AN: 10700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3526

South Asian (SAS) AF: 0.00 AC: 0 AN: 2747

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6148

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53012

Other (OTH) AF: 0.00 AC: 0 AN: 1515

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.40
DANN	Benign	0.84
DEOGEN2	Benign	0.39	T
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	-0.20	N
PhyloP100		0.16
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.21
Sift	Benign	0.21	T
Sift4G	Benign	0.28	T
Polyphen		0.015	B
Vest4		0.045
MutPred		0.28		Gain of loop (P = 0.0045)
MVP		0.45
MPC		0.55
ClinPred		0.0091	T
GERP RS		1.7
Varity_R		0.062
gMVP		0.18
Mutation Taster		=96/4	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: rs782212963; hg19: chrX-153009121;