chrX-153725514-TC-T

Variant names:

• chrX-153725514-TC-T
• rs713993050
• NM_000033.4:c.253delC

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_000033.4(ABCD1):c.253delC (p.Arg85GlyfsTer18) variant causes a frameshift change. The variant is predicted to lead to nonsense-mediated mRNA decay (NMD). The gene ABCD1 is a cancer driver gene (CancerMine: 2 driver citations). The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic/Likely Pathogenic (★★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ABCD1 NM_000033.4 frameshift
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:4
• Conservation: PhyloP100: 1.13
• Publications: 1 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]

ABCD1 Gene-Disease associations (from GenCC):

• adrenoleukodystrophy

  Inheritance: XL, XLR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Natera, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• X-linked cerebral adrenoleukodystrophy

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet
• hereditary spastic paraplegia

  Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp
• Hirschsprung disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• adrenomyeloneuropathy

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

BCAP31 (HGNC:16695): (B cell receptor associated protein 31) This gene encodes a member of the B-cell receptor associated protein 31 superfamily. The encoded protein is a multi-pass transmembrane protein of the endoplasmic reticulum that is involved in the anterograde transport of membrane proteins from the endoplasmic reticulum to the Golgi and in caspase 8-mediated apoptosis. Microdeletions in this gene are associated with contiguous ABCD1/DXS1375E deletion syndrome (CADDS), a neonatal disorder. Alternative splicing of this gene results in multiple transcript variants. Two related pseudogenes have been identified on chromosome 16. [provided by RefSeq, Jan 2012]

BCAP31 Gene-Disease associations (from GenCC):

• severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome

  Inheritance: XL, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000033.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ABCD1 NM_000033.4	MANE Select	c.253delC p.Arg85GlyfsTer18	frameshift	Exon 1 of 10	Prot: NP_000024.2
	ABCD1 NM_001440747.1		c.253delC p.Arg85GlyfsTer18	frameshift	Exon 1 of 11	Prot: NP_001427676.1

ABCD1 NM_000033.4

MANE Select

HGVSc / HGVSpc.253delCp.Arg85GlyfsTer18

Exon rankExon 1 of 10

frameshift

Prot: NP_000024.2

ABCD1 NM_001440747.1

HGVSc / HGVSpc.253delCp.Arg85GlyfsTer18

Exon rankExon 1 of 11

frameshift

Prot: NP_001427676.1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ABCD1 ENST00000218104.6	TSL:1MANE Select	c.253delC p.Arg85GlyfsTer18	frameshift	Exon 1 of 10	Prot: ENSP00000218104.3 UniProt:
	ABCD1 ENST00000862307.1		c.253delC p.Arg85GlyfsTer18	frameshift	Exon 1 of 11	Prot: ENSP00000532366.1 UniProt:
	ABCD1 ENST00000862306.1		c.253delC p.Arg85GlyfsTer18	frameshift	Exon 1 of 11	Prot: ENSP00000532365.1 UniProt:

ABCD1 ENST00000218104.6

TSL:1MANE Select

HGVSc / HGVSpc.253delCp.Arg85GlyfsTer18

Exon rankExon 1 of 10

frameshift

Prot: ENSP00000218104.3UniProt: P33897

ABCD1 ENST00000862307.1

HGVSc / HGVSpc.253delCp.Arg85GlyfsTer18

Exon rankExon 1 of 11

frameshift

Prot: ENSP00000532366.1UniProt: A0ACI8PLS1

ABCD1 ENST00000862306.1

HGVSc / HGVSpc.253delCp.Arg85GlyfsTer18

Exon rankExon 1 of 11

frameshift

Prot: ENSP00000532365.1UniProt: A0ACI8RTK7

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:25
GnomAD4 exome Warning	AF: 0.00	AC:0	Hom:0	AN:1047249	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:25

Showing 3 sources

ClinVar

ClinVar submissions

Significance: Pathogenic/Likely pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
2	-	-	Adrenoleukodystrophy (2)
2	-	-	not provided (2)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	1.1

Showing 1 of 1 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 1 of 1 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs713993050;

hg19: chrX-152990969;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar