Variant rs7122032 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_181507.2(HPS5):c.824+34A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,434,014 control chromosomes in the GnomAD database, including 9,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1585 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8319 hom. )

Consequence

HPS5
NM_181507.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.309

Variant links:

Genes affected

HPS5 (HGNC:17022): (HPS5 biogenesis of lysosomal organelles complex 2 subunit 2) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. This protein interacts with Hermansky-Pudlak syndrome 6 protein and may interact with the cytoplasmic domain of integrin, alpha-3. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 5. Multiple transcript variants encoding two distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

HPS5 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=-0.8).

BP6

Variant 11-18306101-T-G is Benign according to our data. Variant chr11-18306101-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 262988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS5	NM_181507.2 linkuse as main transcript	c.824+34A>C		intron_variant		ENST00000349215.8	NP_852608.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
HPS5	ENST00000349215.8 linkuse as main transcript	c.824+34A>C	intron_variant	1	NM_181507.2	ENSP00000265967	P1	Q9UPZ3-1
HPS5	ENST00000396253.7 linkuse as main transcript	c.482+34A>C	intron_variant	1		ENSP00000379552		Q9UPZ3-2
HPS5	ENST00000438420.6 linkuse as main transcript	c.482+34A>C	intron_variant	1		ENSP00000399590		Q9UPZ3-2
HPS5	ENST00000531848.1 linkuse as main transcript	c.482+34A>C	intron_variant	5		ENSP00000431758

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21213

AN:

152072

Hom.:

1582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.152

GnomAD3 exomes

AF:

0.137

AC:

34279

AN:

250790

Hom.:

2741

AF XY:

0.131

AC XY:

17820

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.119

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.161

Gnomad NFE exome

AF:

0.109

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.107

AC:

136957

AN:

1281824

Hom.:

8319

Cov.:

AF XY:

0.107

AC XY:

69336

AN XY:

647048

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.0922

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.139

AC:

21227

AN:

152190

Hom.:

1585

Cov.:

AF XY:

0.142

AC XY:

10603

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.123

Hom.:

239

Bravo

AF:

0.140

Asia WGS

AF:

0.141

AC:

492

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.7

DANN

Benign

0.51

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