chr3-149167992-A-AT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_032383.5(HPS3):c.2887+19dupT 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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

aceruloplasminemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
disorder of iron metabolism and transport
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
HPS3	NM_032383.5 link	c.2887+19dupT		intron_variant	Intron 16 of 16	ENST00000296051.7	NP_115759.2	Q969F9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS3	ENST00000296051.7 link	c.2887+19dupT		intron_variant	Intron 16 of 16	1	NM_032383.5	ENSP00000296051.2		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

GnomAD2 exomes

AF:

0.325

AC:

67084

AN:

206140

AF XY:

0.321

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 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

African (AFR)

AF:

0.501

AC:

11800

AN:

23574

American (AMR)

AF:

0.224

AC:

9186

AN:

40964

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

4935

AN:

22994

East Asian (EAS)

AF:

0.330

AC:

11681

AN:

35426

South Asian (SAS)

AF:

0.283

AC:

21429

AN:

75646

European-Finnish (FIN)

AF:

0.339

AC:

17071

AN:

50312

Middle Eastern (MID)

AF:

0.218

AC:

1072

AN:

4916

European-Non Finnish (NFE)

AF:

0.254

AC:

211314

AN:

833266

Other (OTH)

AF:

0.278

AC:

13505

AN:

48566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

10295

20589

30884

41178

51473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6584

13168

19752

26336

32920

<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:

0.396

AC:

59523

AN:

150240

Hom.:

13267

Cov.:

AF XY:

0.395

AC XY:

28963

AN XY:

73340

show subpopulations

African (AFR)

AF:

0.617

AC:

25301

AN:

40984

American (AMR)

AF:

0.277

AC:

4168

AN:

15070

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

753

AN:

3432

East Asian (EAS)

AF:

0.372

AC:

1906

AN:

5124

South Asian (SAS)

AF:

0.324

AC:

1547

AN:

4780

European-Finnish (FIN)

AF:

0.391

AC:

3990

AN:

10206

Middle Eastern (MID)

AF:

0.264

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.308

AC:

20772

AN:

67366

Other (OTH)

AF:

0.349

AC:

727

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1610

3220

4830

6440

8050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.224

Hom.:

479

Bravo

AF:

0.395

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 02, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hermansky-Pudlak syndrome

Benign:2

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 25, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

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

PhyloP100

-0.19

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over