Variant rs2689232 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_032383.5(HPS3):c.1164-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,606,278 control chromosomes in the GnomAD database, including 41,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.18 ( 3072 hom., cov: 31)

Exomes 𝑓: 0.22 ( 38449 hom. )

Consequence

HPS3
NM_032383.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.541

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:

HPS3 (HGNC:):

HPS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 3-149150574-C-T is Benign according to our data. Variant chr3-149150574-C-T is described in ClinVar as [Benign]. Clinvar id is 262023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 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.1164-25C>T		intron_variant		ENST00000296051.7	NP_115759.2	Q969F9-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
HPS3	ENST00000296051.7 linkuse as main transcript	c.1164-25C>T	intron_variant	1	NM_032383.5	ENSP00000296051.2	Q969F9-1
HPS3	ENST00000460120.5 linkuse as main transcript	c.669-25C>T	intron_variant	2		ENSP00000418230.1	G5E9V4
HPS3	ENST00000462030.5 linkuse as main transcript	n.1763-25C>T	intron_variant	2
HPS3	ENST00000486530.1 linkuse as main transcript	n.1197-25C>T	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27466

AN:

152034

Hom.:

3075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0657

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.212

AC:

53155

AN:

250742

Hom.:

6242

AF XY:

0.220

AC XY:

29854

AN XY:

135508

show subpopulations

Gnomad AFR exome

AF:

0.0612

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.278

Gnomad SAS exome

AF:

0.292

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.224

AC:

326012

AN:

1454126

Hom.:

38449

Cov.:

AF XY:

0.227

AC XY:

164363

AN XY:

723866

show subpopulations

Gnomad4 AFR exome

AF:

0.0577

Gnomad4 AMR exome

AF:

0.137

Gnomad4 ASJ exome

AF:

0.123

Gnomad4 EAS exome

AF:

0.269

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.264

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.210

GnomAD4 genome

AF:

0.181

AC:

27468

AN:

152152

Hom.:

3072

Cov.:

AF XY:

0.185

AC XY:

13720

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0657

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.282

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.198

Hom.:

632

Bravo

AF:

0.163

Asia WGS

AF:

0.256

AC:

892

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

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

-0.28

CADD

Benign

DANN

Benign

0.77

BranchPoint Hunter

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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