Variant 3-149167290-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032383.5(HPS3):c.2796+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,428,630 control chromosomes in the GnomAD database, including 137,493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17050 hom., cov: 33)

Exomes 𝑓: 0.43 ( 120443 hom. )

Consequence

HPS3
NM_032383.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.213

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 3-149167290-C-T is Benign according to our data. Variant chr3-149167290-C-T is described in ClinVar as [Benign]. Clinvar id is 262024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS3	NM_032383.5 link	c.2796+50C>T		intron_variant		ENST00000296051.7	NP_115759.2	Q969F9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPS3	ENST00000296051.7 link	c.2796+50C>T		intron_variant		1	NM_032383.5	ENSP00000296051.2		Q969F9-1

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70462

AN:

151914

Hom.:

17028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.597

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.441

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.427

AC:

74918

AN:

175478

Hom.:

16836

AF XY:

0.440

AC XY:

41363

AN XY:

94010

show subpopulations

Gnomad AFR exome

AF:

0.605

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.320

Gnomad EAS exome

AF:

0.379

Gnomad SAS exome

AF:

0.582

Gnomad FIN exome

AF:

0.433

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.430

AC:

548806

AN:

1276598

Hom.:

120443

Cov.:

AF XY:

0.435

AC XY:

277929

AN XY:

638964

show subpopulations

Gnomad4 AFR exome

AF:

0.609

Gnomad4 AMR exome

AF:

0.287

Gnomad4 ASJ exome

AF:

0.322

Gnomad4 EAS exome

AF:

0.367

Gnomad4 SAS exome

AF:

0.576

Gnomad4 FIN exome

AF:

0.432

Gnomad4 NFE exome

AF:

0.423

Gnomad4 OTH exome

AF:

0.428

GnomAD4 genome

AF:

0.464

AC:

70531

AN:

152032

Hom.:

17050

Cov.:

AF XY:

0.464

AC XY:

34474

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.597

Gnomad4 AMR

AF:

0.339

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.389

Gnomad4 SAS

AF:

0.577

Gnomad4 FIN

AF:

0.441

Gnomad4 NFE

AF:

0.423

Gnomad4 OTH

AF:

0.417

Alfa

AF:

0.428

Hom.:

11998

Bravo

AF:

0.455

Asia WGS

AF:

0.480

AC:

1670

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Hermansky-Pudlak syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.3

DANN

Benign

0.36

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