X-153743269-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_000033.4(ABCD1):​c.1914C>T​(p.Asp638=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000978 in 1,206,150 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 2 hem., cov: 24)
Exomes 𝑓: 0.00010 ( 0 hom. 39 hem. )

Consequence

ABCD1
NM_000033.4 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -0.429
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]
PLXNB3-AS1 (HGNC:40454): (PLXNB3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant X-153743269-C-T is Benign according to our data. Variant chrX-153743269-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 528350.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.429 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCD1NM_000033.4 linkuse as main transcriptc.1914C>T p.Asp638= synonymous_variant 9/10 ENST00000218104.6 NP_000024.2
ABCD1XM_047441916.1 linkuse as main transcriptc.2214C>T p.Asp738= synonymous_variant 10/11 XP_047297872.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCD1ENST00000218104.6 linkuse as main transcriptc.1914C>T p.Asp638= synonymous_variant 9/101 NM_000033.4 ENSP00000218104 P1
PLXNB3-AS1ENST00000434284.1 linkuse as main transcriptn.72-4691G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000621
AC:
7
AN:
112749
Hom.:
0
Cov.:
24
AF XY:
0.0000573
AC XY:
2
AN XY:
34905
show subpopulations
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000113
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000638
AC:
11
AN:
172412
Hom.:
0
AF XY:
0.0000507
AC XY:
3
AN XY:
59148
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:
0.0000566
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000102
AC:
111
AN:
1093401
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
39
AN XY:
360159
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:
0.0000188
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000120
Gnomad4 OTH exome
AF:
0.000174
GnomAD4 genome
AF:
0.0000621
AC:
7
AN:
112749
Hom.:
0
Cov.:
24
AF XY:
0.0000573
AC XY:
2
AN XY:
34905
show subpopulations
Gnomad4 AFR
AF:
0.0000322
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:
0.000113
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000654
Hom.:
1
Bravo
AF:
0.0000680

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Adrenoleukodystrophy Uncertain:1Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 16, 2024- -
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabNov 07, 2021- -
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 28, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2024ABCD1: BP4, BP7 -
ABCD1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesAug 03, 2022This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
2.1
DANN
Benign
0.93

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.

Other links and lift over

dbSNP: rs199723613; hg19: chrX-153008723; COSMIC: COSV54385996; COSMIC: COSV54385996; API