Genetic Variant ABCD1:p.Tyr666Tyr (chrX-153743495-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000033.4(ABCD1):c.1998C>T(p.Tyr666Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000333 in 1,202,836 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

ABCD1
NM_000033.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.04

Publications

0 publications found

Variant links:

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]

ABCD1 links:

PLXNB3-AS1 (HGNC:40454): (PLXNB3 antisense RNA 1)

PLXNB3-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD1	NM_000033.4 link	c.1998C>T	p.Tyr666Tyr	synonymous_variant	Exon 10 of 10	ENST00000218104.6	NP_000024.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCD1	ENST00000218104.6 link	c.1998C>T	p.Tyr666Tyr	synonymous_variant	Exon 10 of 10	1	NM_000033.4	ENSP00000218104.3
PLXNB3-AS1	ENST00000434284.1 link	n.72-4917G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000970

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

GnomAD4 exome

AF:

9.17e-7

AC:

AN:

1090602

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

358010

show subpopulations

African (AFR)

AF:

0.0000381

AC:

AN:

26276

American (AMR)

AF:

0.00

AC:

AN:

34766

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19219

East Asian (EAS)

AF:

0.00

AC:

AN:

30042

South Asian (SAS)

AF:

0.00

AC:

AN:

53161

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2886

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

838445

Other (OTH)

AF:

0.00

AC:

AN:

45725

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112234

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34410

show subpopulations

African (AFR)

AF:

0.0000970

AC:

AN:

30917

American (AMR)

AF:

0.00

AC:

AN:

10685

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3549

South Asian (SAS)

AF:

0.00

AC:

AN:

2746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53078

Other (OTH)

AF:

0.00

AC:

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

5.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over