Variant 11-18322147-G-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_181508.1(HPS5):c.-249C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,328 control chromosomes in the GnomAD database, including 1,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1554 hom., cov: 32)

Exomes 𝑓: 0.067 ( 1 hom. )

Consequence

HPS5
NM_181508.1 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.29

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:

HPS5 (HGNC:):

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=-0.83).

BP6

Variant 11-18322147-G-T is Benign according to our data. Variant chr11-18322147-G-T is described in ClinVar as [Benign]. Clinvar id is 303906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 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.-251C>A		upstream_gene_variant		ENST00000349215.8	NP_852608.1	Q9UPZ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPS5	ENST00000349215.8 linkuse as main transcript	c.-251C>A		upstream_gene_variant		1	NM_181507.2	ENSP00000265967.5		Q9UPZ3-1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20937

AN:

152030

Hom.:

1551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.0560

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.149

GnomAD4 exome

AF:

0.0667

AC:

AN:

180

Hom.:

Cov.:

AF XY:

0.0870

AC XY:

AN XY:

138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.0455

Gnomad4 OTH exome

AF:

0.0714

GnomAD4 genome

AF:

0.138

AC:

20949

AN:

152148

Hom.:

1554

Cov.:

AF XY:

0.140

AC XY:

10440

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.108

Hom.:

823

Bravo

AF:

0.139

Asia WGS

AF:

0.137

AC:

478

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hermansky-Pudlak syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

DANN

Benign

0.68

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