rs128624222

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP6_Moderate

The NM_000033.4(ABCD1):c.1429G>A(p.Glu477Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000908 in 1,210,992 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. E477E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 0.0000073 ( 0 hom. 4 hem. )

Consequence

ABCD1
NM_000033.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.32

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:

LOC124905226 (HGNC:):

LOC124905226 links:

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

PLXNB3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 4 benign, 5 uncertain in NM_000033.4

BP6

Variant X-153737192-G-A is Benign according to our data. Variant chrX-153737192-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2082210.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABCD1	NM_000033.4 linkuse as main transcript	c.1429G>A	p.Glu477Lys	missense_variant	5/10	ENST00000218104.6
LOC124905226	XR_007068350.1 linkuse as main transcript	n.3159C>T		non_coding_transcript_exon_variant	2/2
ABCD1	XM_047441916.1 linkuse as main transcript	c.1729G>A	p.Glu577Lys	missense_variant	6/11
ABCD1	XM_047441917.1 linkuse as main transcript	c.1485G>A	p.Ala495=	synonymous_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ABCD1	ENST00000218104.6 linkuse as main transcript	c.1429G>A	p.Glu477Lys	missense_variant	5/10	1	NM_000033.4	P1
PLXNB3-AS1	ENST00000434284.1 linkuse as main transcript	n.580+878C>T		intron_variant, non_coding_transcript_variant		3
ABCD1	ENST00000443684.2 linkuse as main transcript	n.432G>A		non_coding_transcript_exon_variant	4/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

113365

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35505

show subpopulations

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:

0.0000562

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000220

AC:

AN:

182081

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67225

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000492

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000729

AC:

AN:

1097627

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363185

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000950

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000265

AC:

AN:

113365

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35505

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000562

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Adrenoleukodystrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Uncertain

0.030

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.52

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.48

MetaRNN

Uncertain

0.46

MetaSVM

Pathogenic

1.2

MutationAssessor

Benign

0.92

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.48

Sift

Benign

0.64

Sift4G

Benign

0.67

Polyphen

0.012

Vest4

0.53

MutPred

0.58

Gain of methylation at E477 (P = 6e-04);

MVP

0.80

MPC

0.64

ClinPred

0.31

GERP RS

4.0

Varity_R

0.39

gMVP

0.84

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over