1-94418487-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_002858.4(ABCD3):c.9C>T(p.Ala3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,601,714 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: ABCD3 NM_002858.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.48

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 1-94418487-C-T is Benign according to our data. Variant chr1-94418487-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1589644.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.48 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCD3	NM_002858.4	c.9C>T	p.Ala3=	synonymous_variant	1/23	ENST00000370214.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCD3	ENST00000370214.9	c.9C>T	p.Ala3=	synonymous_variant	1/23	1	NM_002858.4	P3
ABCD3	ENST00000315713.5	c.9C>T	p.Ala3=	synonymous_variant	1/9	1
ABCD3	ENST00000647998.2	c.9C>T	p.Ala3=	synonymous_variant	1/23			A1

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

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: 0.000309

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000212 AC: 49 AN: 230942 Hom.: 1 AF XY: 0.000236 AC XY: 30 AN XY: 127082

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000443

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000101

Gnomad FIN exome AF: 0.0000663

Gnomad NFE exome AF: 0.000277

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.000135 AC: 195 AN: 1449428 Hom.: 1 Cov.: 31 AF XY: 0.000150 AC XY: 108 AN XY: 721298

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000383

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000350

Gnomad4 FIN exome AF: 0.0000223

Gnomad4 NFE exome AF: 0.000151

Gnomad4 OTH exome AF: 0.0000333

GnomAD4 genome AF: 0.000295 AC: 45 AN: 152286 Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 27 AN XY: 74480

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000186 Hom.: 0

Bravo AF: 0.000280

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	15
Dann	Benign	0.97

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: rs371364095; hg19: chr1-94884043;