X-153743698-C-A

Variant names:

• chrX-153743698-C-A
• rs368462762
• NM_000033.4:c.2201C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000033.4(ABCD1):​c.2201C>A​(p.Pro734Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000893 in 111,964 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 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. P734L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ABCD1 NM_000033.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082030505).

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.2201C>A	p.Pro734Gln	missense	Exon 10 of 10	NP_000024.2
	ABCD1	NM_001440747.1		c.2501C>A	p.Pro834Gln	missense	Exon 11 of 11	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-5120G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.2201C>A	p.Pro734Gln	missense	Exon 10 of 10	ENSP00000218104.3	P33897
	ABCD1	ENST00000862307.1		c.2501C>A	p.Pro834Gln	missense	Exon 11 of 11	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.2471C>A	p.Pro824Gln	missense	Exon 11 of 11	ENSP00000532365.1

Frequencies

GnomAD3 genomes AF: 0.00000893 AC: 1 AN: 111964 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1056178 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 343322

African (AFR) AF: 0.00 AC: 0 AN: 25171

American (AMR) AF: 0.00 AC: 0 AN: 29126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18620

East Asian (EAS) AF: 0.00 AC: 0 AN: 27638

South Asian (SAS) AF: 0.00 AC: 0 AN: 50057

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2860

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 823372

Other (OTH) AF: 0.00 AC: 0 AN: 44478

GnomAD4 genome AF: 0.00000893 AC: 1 AN: 111964 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34162

African (AFR) AF: 0.00 AC: 0 AN: 30843

American (AMR) AF: 0.00 AC: 0 AN: 10676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3517

South Asian (SAS) AF: 0.00 AC: 0 AN: 2732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6147

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

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52966

Other (OTH) AF: 0.00 AC: 0 AN: 1517

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	3.7
DANN	Benign	0.95
DEOGEN2	Benign	0.36	T
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.31	T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.29
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.19	N
REVEL	Uncertain	0.30
Sift	Benign	0.34	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.27		Gain of solvent accessibility (P = 0.0044)
MVP		0.69
MPC		0.54
ClinPred		0.11	T
GERP RS		-0.86
Varity_R		0.038
gMVP		0.18
Mutation Taster		=100/0	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: rs368462762; hg19: chrX-153009152;