1-94464759-C-CT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_002858.4(ABCD3):c.148-8dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000276 in 1,564,910 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00030 (2 hom.)
• Consequence: ABCD3 NM_002858.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.262

Genes affected

ABCD3 (HGNC:67): (ATP binding cassette subfamily D member 3) 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 likely plays an important role in peroxisome biogenesis. Mutations have been associated with some forms of Zellweger syndrome, a heterogeneous group of peroxisome assembly disorders. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 1-94464759-C-CT is Benign according to our data. Variant chr1-94464759-C-CT is described in ClinVar as [Benign]. Clinvar id is 1910050.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCD3	NM_002858.4	c.148-8dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000370214.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCD3	ENST00000370214.9	c.148-8dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002858.4	P3
ABCD3	ENST00000315713.5	c.148-8dup		splice_polypyrimidine_tract_variant, intron_variant		1
ABCD3	ENST00000647998.2	c.148-8dup		splice_polypyrimidine_tract_variant, intron_variant				A1
ABCD3	ENST00000468860.1	n.225-8dup		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0000861 AC: 13 AN: 151036 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000730

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000421

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.0000590

Gnomad OTH AF: 0.000485

GnomAD4 exome AF: 0.000296 AC: 419 AN: 1413758 Hom.: 2 Cov.: 29 AF XY: 0.000282 AC XY: 199 AN XY: 705106

Gnomad4 AFR exome AF: 0.000304

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000391

Gnomad4 EAS exome AF: 0.000102

Gnomad4 SAS exome AF: 0.000294

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000312

Gnomad4 OTH exome AF: 0.000324

GnomAD4 genome AF: 0.0000860 AC: 13 AN: 151152 Hom.: 0 Cov.: 31 AF XY: 0.0000677 AC XY: 5 AN XY: 73802

Gnomad4 AFR AF: 0.0000728

Gnomad4 AMR AF: 0.000132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000421

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000590

Gnomad4 OTH AF: 0.000480

Bravo AF: 0.0000793

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs756130721; hg19: chr1-94930315;