rs199702315

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 179635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-78101011-TTTC-T is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B1	NM_003664.5 link	c.2409_2411delGAA	p.Lys804del	disruptive_inframe_deletion	Exon 21 of 27	ENST00000255194.11	NP_003655.3	O00203-1A0A0S2Z5J4
AP3B1	NM_001271769.2 link	c.2262_2264delGAA	p.Lys755del	disruptive_inframe_deletion	Exon 21 of 27		NP_001258698.1	O00203-3A0A0S2Z5J4
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		O00203-1

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

GnomAD3 exomes

AF:

0.0136

AC:

3069

AN:

226264

Hom.:

AF XY:

0.0133

AC XY:

1621

AN XY:

121804

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 SAS exome

AF:

0.00136

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

Gnomad4 AFR exome

AF:

0.00286

Gnomad4 AMR exome

AF:

0.00605

Gnomad4 ASJ exome

AF:

0.00489

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00134

Gnomad4 FIN exome

AF:

0.0362

Gnomad4 NFE exome

AF:

0.0199

Gnomad4 OTH exome

AF:

0.0160

GnomAD4 genome

AF:

0.0142

AC:

2162

AN:

152258

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1056

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00394

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.0330

Gnomad4 NFE

AF:

0.0200

Gnomad4 OTH

AF:

0.0123

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

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