rs337592

Variant names:

• chr1-94517254-A-G
• rs337592
• NM_002858.4:c.*125A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

ABCD3 Gene-Disease associations (from GenCC):

• congenital bile acid synthesis defect 5

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002858.4. 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
	ABCD3	NM_002858.4	MANE Select	c.*125A>G		3_prime_UTR	Exon 23 of 23	NP_002849.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD3	ENST00000370214.9	TSL:1 MANE Select	c.*125A>G		3_prime_UTR	Exon 23 of 23	ENSP00000359233.4
	ABCD3	ENST00000484213.1	TSL:1	n.2955A>G		non_coding_transcript_exon	Exon 14 of 14
	ABCD3	ENST00000866889.1		c.*125A>G		3_prime_UTR	Exon 24 of 24	ENSP00000536948.1

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

African (AFR) AF: 0.137 AC: 1998 AN: 14588

American (AMR) AF: 0.0313 AC: 962 AN: 30784

Ashkenazi Jewish (ASJ) AF: 0.0583 AC: 1060 AN: 18172

East Asian (EAS) AF: 0.116 AC: 3777 AN: 32688

South Asian (SAS) AF: 0.118 AC: 7098 AN: 60382

European-Finnish (FIN) AF: 0.136 AC: 5416 AN: 39958

Middle Eastern (MID) AF: 0.0473 AC: 117 AN: 2472

European-Non Finnish (NFE) AF: 0.0556 AC: 19146 AN: 344056

Other (OTH) AF: 0.0780 AC: 2327 AN: 29846

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

African (AFR) AF: 0.135 AC: 5620 AN: 41478

American (AMR) AF: 0.0484 AC: 737 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0682 AC: 236 AN: 3462

East Asian (EAS) AF: 0.126 AC: 652 AN: 5168

South Asian (SAS) AF: 0.123 AC: 593 AN: 4818

European-Finnish (FIN) AF: 0.137 AC: 1450 AN: 10568

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0578 AC: 3917 AN: 67778

Other (OTH) AF: 0.0678 AC: 143 AN: 2108

Alfa AF: 0.0730 Hom.: 271

Bravo AF: 0.0816

Asia WGS AF: 0.145 AC: 500 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.8
DANN	Benign	0.80
PhyloP100		0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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