rs42360

Variant names:

Variant summary

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

The NM_003664.5(AP3B1):c.2016T>C(p.Ala672Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,612,438 control chromosomes in the GnomAD database, including 44,621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4353 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40268 hom. )

Consequence

AP3B1
NM_003664.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 0.738

Publications

19 publications found

Variant links:

Genes affected

AP3B1 (HGNC:566): (adaptor related protein complex 3 subunit beta 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is part of the heterotetrameric AP-3 protein complex which interacts with the scaffolding protein clathrin. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

AP3B1 Gene-Disease associations (from GenCC):

Hermansky-Pudlak syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

AP3B1 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=-0.46).

BP6

Variant 5-78116187-A-G is Benign according to our data. Variant chr5-78116187-A-G is described in ClinVar as [Benign]. Clinvar id is 162752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.738 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B1	NM_003664.5 link	c.2016T>C	p.Ala672Ala	synonymous_variant	Exon 18 of 27	ENST00000255194.11	NP_003655.3	O00203-1A0A0S2Z5J4
AP3B1	NM_001271769.2 link	c.1869T>C	p.Ala623Ala	synonymous_variant	Exon 18 of 27		NP_001258698.1	O00203-3A0A0S2Z5J4
AP3B1	NM_001410752.1 link	c.2016T>C	p.Ala672Ala	synonymous_variant	Exon 18 of 23		NP_001397681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11 link	c.2016T>C	p.Ala672Ala	synonymous_variant	Exon 18 of 27	1	NM_003664.5	ENSP00000255194.7		O00203-1

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35496

AN:

152032

Hom.:

4349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.0703

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.230

GnomAD2 exomes

AF:

0.213

AC:

53518

AN:

251274

AF XY:

0.205

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.0598

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.233

Gnomad OTH exome

AF:

0.221

GnomAD4 exome

AF:

0.229

AC:

334316

AN:

1460288

Hom.:

40268

Cov.:

AF XY:

0.225

AC XY:

163524

AN XY:

726512

show subpopulations

African (AFR)

AF:

0.261

AC:

8720

AN:

33440

American (AMR)

AF:

0.311

AC:

13894

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

4742

AN:

26110

East Asian (EAS)

AF:

0.0758

AC:

3006

AN:

39638

South Asian (SAS)

AF:

0.128

AC:

11058

AN:

86238

European-Finnish (FIN)

AF:

0.179

AC:

9531

AN:

53356

Middle Eastern (MID)

AF:

0.136

AC:

784

AN:

5762

European-Non Finnish (NFE)

AF:

0.243

AC:

269554

AN:

1110690

Other (OTH)

AF:

0.216

AC:

13027

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

12456

24912

37367

49823

62279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.234

AC:

35534

AN:

152150

Hom.:

4353

Cov.:

AF XY:

0.229

AC XY:

17064

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.256

AC:

10607

AN:

41500

American (AMR)

AF:

0.310

AC:

4733

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

572

AN:

3466

East Asian (EAS)

AF:

0.0697

AC:

361

AN:

5182

South Asian (SAS)

AF:

0.132

AC:

635

AN:

4828

European-Finnish (FIN)

AF:

0.169

AC:

1788

AN:

10602

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16151

AN:

67990

Other (OTH)

AF:

0.234

AC:

494

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1389

2778

4168

5557

6946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.234

Hom.:

8072

Bravo

AF:

0.244

Asia WGS

AF:

0.145

AC:

506

AN:

3474

EpiCase

AF:

0.232

EpiControl

AF:

0.233

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ala672Ala in exon 18 of AP3B1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 25.8% (1135/4406) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs42360). -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 46% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. Only high quality variants are reported. -

Feb 09, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2Other:1

Nov 27, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hermansky-Pudlak syndrome 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hermansky-Pudlak syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.3

(source)

DANN

Benign

0.71

PhyloP100

0.74

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs42360

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over