Variant chr3-149150460-A-C 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.1164-139A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 710,720 control chromosomes in the GnomAD database, including 158,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 37791 hom., cov: 31)

Exomes 𝑓: 0.65 ( 120828 hom. )

Consequence

HPS3
NM_032383.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.56

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 3-149150460-A-C is Benign according to our data. Variant chr3-149150460-A-C is described in ClinVar as [Benign]. Clinvar id is 1185217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 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.1164-139A>C		intron_variant		ENST00000296051.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
HPS3	ENST00000296051.7 linkuse as main transcript	c.1164-139A>C	intron_variant	1	NM_032383.5	P1	Q969F9-1
HPS3	ENST00000460120.5 linkuse as main transcript	c.669-139A>C	intron_variant	2
HPS3	ENST00000462030.5 linkuse as main transcript	n.1763-139A>C	intron_variant, non_coding_transcript_variant	2
HPS3	ENST00000486530.1 linkuse as main transcript	n.1197-139A>C	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.696

AC:

105684

AN:

151878

Hom.:

37734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.857

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.582

Gnomad ASJ

AF:

0.560

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.793

Gnomad FIN

AF:

0.732

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.636

Gnomad OTH

AF:

0.630

GnomAD4 exome

AF:

0.652

AC:

364397

AN:

558724

Hom.:

120828

AF XY:

0.660

AC XY:

198570

AN XY:

301022

show subpopulations

Gnomad4 AFR exome

AF:

0.855

Gnomad4 AMR exome

AF:

0.561

Gnomad4 ASJ exome

AF:

0.564

Gnomad4 EAS exome

AF:

0.532

Gnomad4 SAS exome

AF:

0.781

Gnomad4 FIN exome

AF:

0.718

Gnomad4 NFE exome

AF:

0.637

Gnomad4 OTH exome

AF:

0.642

GnomAD4 genome

AF:

0.696

AC:

105797

AN:

151996

Hom.:

37791

Cov.:

AF XY:

0.699

AC XY:

51870

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.857

Gnomad4 AMR

AF:

0.581

Gnomad4 ASJ

AF:

0.560

Gnomad4 EAS

AF:

0.533

Gnomad4 SAS

AF:

0.793

Gnomad4 FIN

AF:

0.732

Gnomad4 NFE

AF:

0.636

Gnomad4 OTH

AF:

0.633

Alfa

AF:

0.635

Hom.:

49766

Bravo

AF:

0.685

Asia WGS

AF:

0.698

AC:

2428

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hermansky-Pudlak syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

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

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.28

DANN

Benign

0.65

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