rs337592

Positions:

• chr1-94517254-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002858.4(ABCD3):​c.*125A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 724,756 control chromosomes in the GnomAD database, including 2,689 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.088 (693 hom., cov: 32)
  • Exomes 𝑓: 0.073 (1996 hom.)
• Consequence: ABCD3 NM_002858.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.807

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCD3	NM_002858.4	c.*125A>G		3_prime_UTR_variant	23/23	ENST00000370214.9	NP_002849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCD3	ENST00000370214.9	c.*125A>G		3_prime_UTR_variant	23/23	1	NM_002858.4	ENSP00000359233.4
ABCD3	ENST00000484213.1	n.2955A>G		non_coding_transcript_exon_variant	14/14	1
ABCD3	ENST00000647998.2	c.*125A>G		3_prime_UTR_variant	23/23			ENSP00000497921.2
ABCD3	ENST00000464165.1	n.1932A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0885 AC: 13427 AN: 151692 Hom.: 693 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0682

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0578

Gnomad OTH AF: 0.0652

GnomAD4 exome AF: 0.0731 AC: 41901 AN: 572946 Hom.: 1996 Cov.: 7 AF XY: 0.0748 AC XY: 23283 AN XY: 311228

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0313

Gnomad4 ASJ exome AF: 0.0583

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.0556

Gnomad4 OTH exome AF: 0.0780

GnomAD4 genome AF: 0.0885 AC: 13433 AN: 151810 Hom.: 693 Cov.: 32 AF XY: 0.0918 AC XY: 6815 AN XY: 74214

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0484

Gnomad4 ASJ AF: 0.0682

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0578

Gnomad4 OTH AF: 0.0678

Alfa AF: 0.0734 Hom.: 173

Bravo AF: 0.0816

Asia WGS AF: 0.145 AC: 500 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.8
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs337592; hg19: chr1-94982810; COSMIC: COSV64643980;