1-94464782-G-T

Position:

chr1-94464782-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.65

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCD3	NM_002858.4 linkuse as main transcript	c.155G>T	p.Gly52Val	missense_variant	3/23	ENST00000370214.9	NP_002849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCD3	ENST00000370214.9 linkuse as main transcript	c.155G>T	p.Gly52Val	missense_variant	3/23	1	NM_002858.4	ENSP00000359233	P3	P28288-1
ABCD3	ENST00000315713.5 linkuse as main transcript	c.155G>T	p.Gly52Val	missense_variant	3/9	1		ENSP00000326880		P28288-3
ABCD3	ENST00000647998.2 linkuse as main transcript	c.155G>T	p.Gly52Val	missense_variant	3/23			ENSP00000497921	A1
ABCD3	ENST00000468860.1 linkuse as main transcript	n.232G>T		non_coding_transcript_exon_variant	4/8	3

Frequencies

GnomAD3 genomes

AF:

0.00503

AC:

763

AN:

151602

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00555

AC XY:

754

AN XY:

135808

show subpopulations

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.:

Cov.:

AF XY:

0.00419

AC XY:

3044

AN XY:

726998

show subpopulations

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.:

Cov.:

AF XY:

0.00675

AC XY:

500

AN XY:

74128

show subpopulations

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.:

Bravo

AF:

0.00205

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00372

AC:

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.42

.;T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.84

.;T;T

MetaRNN

Benign

0.0073

T;T;T

MetaSVM

Uncertain

0.77

MutationAssessor

Benign

1.3

.;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.6

.;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.081

.;T;T

Sift4G

Benign

0.31

.;T;T

Polyphen

0.0010, 0.012

.;B;B

Vest4

0.27, 0.26

MVP

0.70

MPC

0.71

ClinPred

0.022

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over