rs199702315

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2

The NM_003664.5(AP3B1):c.2409_2411delGAA(p.Lys804del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,523,058 control chromosomes in the GnomAD database, including 294 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 28 hom., cov: 32)

Exomes 𝑓: 0.018 ( 266 hom. )

Consequence

AP3B1
NM_003664.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.78

Publications

7 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 -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_003664.5. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 5-78101011-TTTC-T is Benign according to our data. Variant chr5-78101011-TTTC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 179635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0142 (2162/152258) while in subpopulation NFE AF = 0.02 (1358/67960). AF 95% confidence interval is 0.0191. There are 28 homozygotes in GnomAd4. There are 1056 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
AP3B1	NM_003664.5 link	c.2409_2411delGAA	p.Lys804del	disruptive_inframe_deletion	Exon 21 of 27	ENST00000255194.11	NP_003655.3
AP3B1	NM_001271769.2 link	c.2262_2264delGAA	p.Lys755del	disruptive_inframe_deletion	Exon 21 of 27		NP_001258698.1
AP3B1	NM_001410752.1 link	c.2409_2411delGAA	p.Lys804del	disruptive_inframe_deletion	Exon 21 of 23		NP_001397681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11 link	c.2409_2411delGAA	p.Lys804del	disruptive_inframe_deletion	Exon 21 of 27	1	NM_003664.5	ENSP00000255194.7

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2165

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00396

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0330

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0200

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.0136

AC:

3069

AN:

226264

AF XY:

0.0133

show subpopulations

Gnomad AFR exome

AF:

0.00338

Gnomad AMR exome

AF:

0.00649

Gnomad ASJ exome

AF:

0.00507

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0354

Gnomad NFE exome

AF:

0.0192

Gnomad OTH exome

AF:

0.0156

GnomAD4 exome

AF:

0.0175

AC:

24053

AN:

1370800

Hom.:

266

AF XY:

0.0172

AC XY:

11757

AN XY:

684740

show subpopulations

African (AFR)

AF:

0.00286

AC:

AN:

31506

American (AMR)

AF:

0.00605

AC:

260

AN:

42994

Ashkenazi Jewish (ASJ)

AF:

0.00489

AC:

123

AN:

25168

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38878

South Asian (SAS)

AF:

0.00134

AC:

109

AN:

81568

European-Finnish (FIN)

AF:

0.0362

AC:

1891

AN:

52284

Middle Eastern (MID)

AF:

0.00412

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

0.0199

AC:

20641

AN:

1035558

Other (OTH)

AF:

0.0160

AC:

915

AN:

57262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.423

Heterozygous variant carriers

956

1913

2869

3826

4782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.0142

AC:

2162

AN:

152258

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1056

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00394

AC:

164

AN:

41582

American (AMR)

AF:

0.0111

AC:

170

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00807

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0330

AC:

350

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0200

AC:

1358

AN:

67960

Other (OTH)

AF:

0.0123

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

103

206

308

411

514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0154

Hom.:

Bravo

AF:

0.0123

Asia WGS

AF:

0.00145

AC:

AN:

3458

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 10, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Lys804del in exon 21 of AP3B1: This variant is not expected to have clinical sig nificance because it has been identified in 1.85% (161/8721) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs199702315). -

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

- -

not provided

Benign:1

Aug 24, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hermansky-Pudlak syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autoinflammatory syndrome

Benign:1

Feb 19, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.8

Mutation Taster

=78/22

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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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