1-94464782-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002858.4(ABCD3):c.155G>T(p.Gly52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,613,052 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0050 (14 hom., cov: 31)
  • Exomes 𝑓: 0.0043 (42 hom.)
• Consequence: ABCD3 NM_002858.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.65

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0072921216).
• BP6: Variant 1-94464782-G-T is Benign according to our data. Variant chr1-94464782-G-T is described in ClinVar as [Benign]. Clinvar id is 718421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCD3	NM_002858.4	c.155G>T	p.Gly52Val	missense_variant	3/23	ENST00000370214.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCD3	ENST00000370214.9	c.155G>T	p.Gly52Val	missense_variant	3/23	1	NM_002858.4	P3
ABCD3	ENST00000315713.5	c.155G>T	p.Gly52Val	missense_variant	3/9	1
ABCD3	ENST00000647998.2	c.155G>T	p.Gly52Val	missense_variant	3/23			A1
ABCD3	ENST00000468860.1	n.232G>T		non_coding_transcript_exon_variant	4/8	3

Frequencies

GnomAD3 genomes AF: 0.00503 AC: 763 AN: 151602 Hom.: 14 Cov.: 31

Gnomad AFR AF: 0.000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000658

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00167

Gnomad FIN AF: 0.0410

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00413

Gnomad OTH AF: 0.00481

GnomAD3 exomes AF: 0.00556 AC: 1396 AN: 251286 Hom.: 24 AF XY: 0.00555 AC XY: 754 AN XY: 135808

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000850

Gnomad FIN exome AF: 0.0380

Gnomad NFE exome AF: 0.00420

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00432 AC: 6312 AN: 1461332 Hom.: 42 Cov.: 30 AF XY: 0.00419 AC XY: 3044 AN XY: 726998

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000731

Gnomad4 FIN exome AF: 0.0344

Gnomad4 NFE exome AF: 0.00377

Gnomad4 OTH exome AF: 0.00257

GnomAD4 genome AF: 0.00503 AC: 763 AN: 151720 Hom.: 14 Cov.: 31 AF XY: 0.00675 AC XY: 500 AN XY: 74128

Gnomad4 AFR AF: 0.000484

Gnomad4 AMR AF: 0.000657

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00168

Gnomad4 FIN AF: 0.0410

Gnomad4 NFE AF: 0.00414

Gnomad4 OTH AF: 0.00476

Alfa AF: 0.00315 Hom.: 0

Bravo AF: 0.00205

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00372 AC: 32

ExAC AF: 0.00502 AC: 610

EpiCase AF: 0.00365

EpiControl AF: 0.00320

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 15, 2023

- -

Congenital bile acid synthesis defect 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Uncertain	0.0
Cadd	Benign	19
Dann	Uncertain	0.98
Eigen	Benign	-0.11
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.69	D
MetaRNN	Benign	0.0073	T;T;T
MetaSVM	Uncertain	0.77	D
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.60	T
Polyphen		0.0010, 0.012	.;B;B
Vest4		0.27, 0.26
MVP		0.70
MPC		0.71
ClinPred		0.022	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.61

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: rs142075958; hg19: chr1-94930338;