X-153736105-T-G

Variant names:

• chrX-153736105-T-G
• NM_000033.4:c.1082-7T>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000033.4(ABCD1):​c.1082-7T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ABCD1 NM_000033.4 splice_region, intron
• Scores: Splicing: ADA: 0.002068
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.972
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-153736105-T-G is Benign according to our data. Variant chrX-153736105-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3020310.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1082-7T>G		splice_region intron	N/A	NP_000024.2
	ABCD1	NM_001440747.1		c.1082-7T>G		splice_region intron	N/A	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.2563A>C		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.1082-7T>G		splice_region intron	N/A	ENSP00000218104.3	P33897
	ABCD1	ENST00000862307.1		c.1082-7T>G		splice_region intron	N/A	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.1082-7T>G		splice_region intron	N/A	ENSP00000532365.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 108690 Hom.: 0 Cov.: 25

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 878017 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 275749

African (AFR) AF: 0.00 AC: 0 AN: 20585

American (AMR) AF: 0.00 AC: 0 AN: 31318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14412

East Asian (EAS) AF: 0.00 AC: 0 AN: 18431

South Asian (SAS) AF: 0.00 AC: 0 AN: 51068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27305

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3209

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 677296

Other (OTH) AF: 0.00 AC: 0 AN: 34393

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 108765 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 32953

African (AFR) AF: 0.00 AC: 0 AN: 30264

American (AMR) AF: 0.00 AC: 0 AN: 10414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2605

East Asian (EAS) AF: 0.00 AC: 0 AN: 3123

South Asian (SAS) AF: 0.00 AC: 0 AN: 2309

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5481

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 213

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52192

Other (OTH) AF: 0.00 AC: 0 AN: 1501

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Adrenoleukodystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.62
PhyloP100		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0021
dbscSNV1_RF	Benign	0.098
SpliceAI score (max)		0.12		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

hg19: chrX-153001559;