Variant rs564039434 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_032383.5(HPS3):c.2887+19dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13267 hom., cov: 0)

Exomes 𝑓: 0.27 ( 23925 hom. )

Consequence

HPS3
NM_032383.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.188

Variant links:

Genes affected

HPS3 (HGNC:15597): (HPS3 biogenesis of lysosomal organelles complex 2 subunit 1) This gene encodes a protein containing a potential clathrin-binding motif, consensus dileucine signals, and tyrosine-based sorting signals for targeting to vesicles of lysosomal lineage. The encoded protein may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 3. [provided by RefSeq, Apr 2015]

HPS3 links:

CP (HGNC:2295): (ceruloplasmin) The protein encoded by this gene is a metalloprotein that binds most of the copper in plasma and is involved in the peroxidation of Fe(II)transferrin to Fe(III) transferrin. Mutations in this gene cause aceruloplasminemia, which results in iron accumulation and tissue damage, and is associated with diabetes and neurologic abnormalities. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]

CP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 3-149167992-A-AT is Benign according to our data. Variant chr3-149167992-A-AT is described in ClinVar as [Benign]. Clinvar id is 343715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS3	NM_032383.5 linkuse as main transcript	c.2887+19dup		intron_variant		ENST00000296051.7	NP_115759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPS3	ENST00000296051.7 linkuse as main transcript	c.2887+19dup		intron_variant		1	NM_032383.5	ENSP00000296051	P1	Q969F9-1

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

59442

AN:

150124

Hom.:

13246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.312

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.260

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.351

GnomAD3 exomes

AF:

0.325

AC:

67084

AN:

206140

Hom.:

6184

AF XY:

0.321

AC XY:

35885

AN XY:

111620

show subpopulations

Gnomad AFR exome

AF:

0.549

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.363

Gnomad SAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.315

GnomAD4 exome

AF:

0.266

AC:

301993

AN:

1135664

Hom.:

23925

Cov.:

AF XY:

0.268

AC XY:

154544

AN XY:

576444

show subpopulations

Gnomad4 AFR exome

AF:

0.501

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.215

Gnomad4 EAS exome

AF:

0.330

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.339

Gnomad4 NFE exome

AF:

0.254

Gnomad4 OTH exome

AF:

0.278

GnomAD4 genome

AF:

0.396

AC:

59523

AN:

150240

Hom.:

13267

Cov.:

AF XY:

0.395

AC XY:

28963

AN XY:

73340

show subpopulations

Gnomad4 AFR

AF:

0.617

Gnomad4 AMR

AF:

0.277

Gnomad4 ASJ

AF:

0.219

Gnomad4 EAS

AF:

0.372

Gnomad4 SAS

AF:

0.324

Gnomad4 FIN

AF:

0.391

Gnomad4 NFE

AF:

0.308

Gnomad4 OTH

AF:

0.349

Bravo

AF:

0.395

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hermansky-Pudlak syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 02, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 25, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency, outside ROI -

Deficiency of ferroxidase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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