1-94464789-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002858.4(ABCD3):c.162G>A(p.Lys54Lys) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.42

Publications

26 publications found

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 Gene-Disease associations (from GenCC):

congenital bile acid synthesis defect 5
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ABCD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD3	NM_002858.4	MANE Select	c.162G>A	p.Lys54Lys	synonymous	Exon 3 of 23	NP_002849.1
	ABCD3	NM_001122674.2		c.162G>A	p.Lys54Lys	synonymous	Exon 3 of 9	NP_001116146.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCD3	ENST00000370214.9	TSL:1 MANE Select	c.162G>A	p.Lys54Lys	synonymous	Exon 3 of 23	ENSP00000359233.4
ABCD3	ENST00000315713.5	TSL:1	c.162G>A	p.Lys54Lys	synonymous	Exon 3 of 9	ENSP00000326880.5
ABCD3	ENST00000647998.2		c.162G>A	p.Lys54Lys	synonymous	Exon 3 of 23	ENSP00000497921.2

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54612

AN:

151410

Hom.:

11397

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.397

AC:

99653

AN:

251194

AF XY:

0.406

show subpopulations

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 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.:

AF XY:

0.453

AC XY:

329024

AN XY:

726188

show subpopulations

African (AFR)

AF:

0.142

AC:

4751

AN:

33434

American (AMR)

AF:

0.380

AC:

16983

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.449

AC:

11708

AN:

26104

East Asian (EAS)

AF:

0.221

AC:

8754

AN:

39674

South Asian (SAS)

AF:

0.372

AC:

32062

AN:

86166

European-Finnish (FIN)

AF:

0.366

AC:

19543

AN:

53408

Middle Eastern (MID)

AF:

0.540

AC:

3111

AN:

5762

European-Non Finnish (NFE)

AF:

0.486

AC:

539008

AN:

1109784

Other (OTH)

AF:

0.439

AC:

26501

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

18042

36083

54125

72166

90208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15556

31112

46668

62224

77780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.361

AC:

54626

AN:

151528

Hom.:

11402

Cov.:

AF XY:

0.354

AC XY:

26236

AN XY:

74018

show subpopulations

African (AFR)

AF:

0.153

AC:

6329

AN:

41312

American (AMR)

AF:

0.407

AC:

6186

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

1520

AN:

3466

East Asian (EAS)

AF:

0.214

AC:

1097

AN:

5126

South Asian (SAS)

AF:

0.349

AC:

1675

AN:

4798

European-Finnish (FIN)

AF:

0.367

AC:

3831

AN:

10452

Middle Eastern (MID)

AF:

0.552

AC:

160

AN:

290

European-Non Finnish (NFE)

AF:

0.476

AC:

32345

AN:

67884

Other (OTH)

AF:

0.424

AC:

889

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1579

3158

4737

6316

7895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.453

Hom.:

31638

Bravo

AF:

0.359

Asia WGS

AF:

0.257

AC:

896

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Oct 22, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Congenital bile acid synthesis defect 5

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

4.3

(source)

DANN

Benign

0.60

PhyloP100

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over