dbSNP rs147055150: ABCD3:p.Gly643Gly (chr1-94517078-C-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7

The NM_002858.4(ABCD3):c.1929C>G(p.Gly643Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,610,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

ABCD3
NM_002858.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.705

Publications

0 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ABCD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 1-94517078-C-G is Benign according to our data. Variant chr1-94517078-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 258822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.705 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD3	NM_002858.4	MANE Select	c.1929C>G	p.Gly643Gly	synonymous	Exon 23 of 23	NP_002849.1	P28288-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCD3	ENST00000370214.9	TSL:1 MANE Select	c.1929C>G	p.Gly643Gly	synonymous	Exon 23 of 23	ENSP00000359233.4	P28288-1
ABCD3	ENST00000484213.1	TSL:1	n.2779C>G		non_coding_transcript_exon	Exon 14 of 14
ABCD3	ENST00000866889.1		c.2001C>G	p.Gly667Gly	synonymous	Exon 24 of 24	ENSP00000536948.1

Frequencies

GnomAD3 genomes

AF:

0.000554

AC:

AN:

151742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000132

AC:

AN:

250712

AF XY:

0.0000664

show subpopulations

Gnomad AFR exome

AF:

0.00179

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000541

AC:

AN:

1459082

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

725908

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

33344

American (AMR)

AF:

0.000134

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39602

South Asian (SAS)

AF:

0.00

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109832

Other (OTH)

AF:

0.000116

AC:

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000553

AC:

AN:

151860

Hom.:

Cov.:

AF XY:

0.000579

AC XY:

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41464

American (AMR)

AF:

0.0000657

AC:

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67826

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000304

Hom.:

Bravo

AF:

0.000676

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.2

(source)

DANN

Benign

0.68

PhyloP100

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over