Variant chr3-149162442-CAG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_032383.5(HPS3):c.2292+111_2292+112del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,047,440 control chromosomes in the GnomAD database, including 10,883 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2558 hom., cov: 29)

Exomes 𝑓: 0.13 ( 8325 hom. )

Consequence

HPS3
NM_032383.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.121

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 -10 ACMG points.

BP6

Variant 3-149162442-CAG-C is Benign according to our data. Variant chr3-149162442-CAG-C is described in ClinVar as [Benign]. Clinvar id is 1268637.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPS3	NM_032383.5 linkuse as main transcript	c.2292+111_2292+112del		intron_variant		ENST00000296051.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPS3	ENST00000296051.7 linkuse as main transcript	c.2292+111_2292+112del		intron_variant		1	NM_032383.5	P1	Q969F9-1

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25965

AN:

151958

Hom.:

2555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.0780

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.0878

Gnomad SAS

AF:

0.0961

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.158

GnomAD3 exomes

AF:

0.132

AC:

22370

AN:

169590

Hom.:

1670

AF XY:

0.130

AC XY:

11962

AN XY:

92062

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.0806

Gnomad SAS exome

AF:

0.0969

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.131

AC:

117201

AN:

895364

Hom.:

8325

AF XY:

0.129

AC XY:

59860

AN XY:

464852

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.0987

Gnomad4 SAS exome

AF:

0.0989

Gnomad4 FIN exome

AF:

0.151

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.171

AC:

25972

AN:

152076

Hom.:

2558

Cov.:

AF XY:

0.169

AC XY:

12577

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.0876

Gnomad4 SAS

AF:

0.0970

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.153

Hom.:

365

Bravo

AF:

0.176

Asia WGS

AF:

0.104

AC:

362

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

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