1-94464789-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002858.4(ABCD3):c.162G>A(p.Lys54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,610,872 control chromosomes in the GnomAD database, including 166,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11402 hom., cov: 29)
  • Exomes 𝑓: 0.45 (155487 hom.)
• Consequence: ABCD3 NM_002858.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.42

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 1-94464789-G-A is Benign according to our data. Variant chr1-94464789-G-A is described in ClinVar as [Benign]. Clinvar id is 258821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.42 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCD3	NM_002858.4	c.162G>A	p.Lys54=	synonymous_variant	3/23	ENST00000370214.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCD3	ENST00000370214.9	c.162G>A	p.Lys54=	synonymous_variant	3/23	1	NM_002858.4	P3
ABCD3	ENST00000315713.5	c.162G>A	p.Lys54=	synonymous_variant	3/9	1
ABCD3	ENST00000647998.2	c.162G>A	p.Lys54=	synonymous_variant	3/23			A1
ABCD3	ENST00000468860.1	n.239G>A		non_coding_transcript_exon_variant	4/8	3

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54612 AN: 151410 Hom.: 11397 Cov.: 29

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.431

GnomAD3 exomes AF: 0.397 AC: 99653 AN: 251194 Hom.: 21200 AF XY: 0.406 AC XY: 55181 AN XY: 135750

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.207

Gnomad SAS exome AF: 0.364

Gnomad FIN exome AF: 0.368

Gnomad NFE exome AF: 0.476

Gnomad OTH exome AF: 0.445

GnomAD4 exome AF: 0.454 AC: 662421 AN: 1459344 Hom.: 155487 Cov.: 36 AF XY: 0.453 AC XY: 329024 AN XY: 726188

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.380

Gnomad4 ASJ exome AF: 0.449

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.366

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.439

GnomAD4 genome AF: 0.361 AC: 54626 AN: 151528 Hom.: 11402 Cov.: 29 AF XY: 0.354 AC XY: 26236 AN XY: 74018

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.424

Alfa AF: 0.460 Hom.: 26592

Bravo AF: 0.359

Asia WGS AF: 0.257 AC: 896 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Congenital bile acid synthesis defect 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	4.3
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16946; hg19: chr1-94930345; COSMIC: COSV59866435;