Variant 10-98429381-A-G 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 ENST00000338546.9(HPS1):c.*154T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 1,525,900 control chromosomes in the GnomAD database, including 229,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 22256 hom., cov: 33)

Exomes 𝑓: 0.55 ( 207087 hom. )

Consequence

HPS1
ENST00000338546.9 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0810

Variant links:

Genes affected

HPS1 (HGNC:5163): (HPS1 biogenesis of lysosomal organelles complex 3 subunit 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is a component of three different protein complexes termed biogenesis of lysosome-related organelles complex (BLOC)-3, BLOC4, and BLOC5. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 1. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on chromosome 22. [provided by RefSeq, Aug 2015]

HPS1 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=-0.86).

BP6

Variant 10-98429381-A-G is Benign according to our data. Variant chr10-98429381-A-G is described in ClinVar as [Benign]. Clinvar id is 1180570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPS1	NM_000195.5 linkuse as main transcript	c.937+192T>C		intron_variant		ENST00000361490.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPS1	ENST00000361490.9 linkuse as main transcript	c.937+192T>C		intron_variant		1	NM_000195.5	P1	Q92902-1

Frequencies

GnomAD3 genomes

AF:

0.540

AC:

82038

AN:

151912

Hom.:

22240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.518

Gnomad AMR

AF:

0.548

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.614

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.625

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.533

GnomAD4 exome

AF:

0.548

AC:

752256

AN:

1373870

Hom.:

207087

Cov.:

AF XY:

0.550

AC XY:

372478

AN XY:

676650

show subpopulations

Gnomad4 AFR exome

AF:

0.488

Gnomad4 AMR exome

AF:

0.550

Gnomad4 ASJ exome

AF:

0.581

Gnomad4 EAS exome

AF:

0.610

Gnomad4 SAS exome

AF:

0.622

Gnomad4 FIN exome

AF:

0.608

Gnomad4 NFE exome

AF:

0.538

Gnomad4 OTH exome

AF:

0.557

GnomAD4 genome

AF:

0.540

AC:

82106

AN:

152030

Hom.:

22256

Cov.:

AF XY:

0.550

AC XY:

40876

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.491

Gnomad4 AMR

AF:

0.548

Gnomad4 ASJ

AF:

0.580

Gnomad4 EAS

AF:

0.614

Gnomad4 SAS

AF:

0.623

Gnomad4 FIN

AF:

0.625

Gnomad4 NFE

AF:

0.542

Gnomad4 OTH

AF:

0.530

Alfa

AF:

0.543

Hom.:

30832

Bravo

AF:

0.529

Asia WGS

AF:

0.585

AC:

2033

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hermansky-Pudlak syndrome 1

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

-0.86

CADD

Benign

7.1

DANN

Benign

0.75

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