Variant rs186991064 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_181507.2(HPS5):c.825-16T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,556,020 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

HPS5
NM_181507.2 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.50

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 11-18305509-A-G is Benign according to our data. Variant chr11-18305509-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 262989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-18305509-A-G is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS5	NM_181507.2 linkuse as main transcript	c.825-16T>C		splice_polypyrimidine_tract_variant, 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.825-16T>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_181507.2	ENSP00000265967	P1	Q9UPZ3-1
HPS5	ENST00000396253.7 linkuse as main transcript	c.483-16T>C	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000379552		Q9UPZ3-2
HPS5	ENST00000438420.6 linkuse as main transcript	c.483-16T>C	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000399590		Q9UPZ3-2
HPS5	ENST00000531848.1 linkuse as main transcript	c.483-16T>C	splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000431758

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00133

AC:

334

AN:

250618

Hom.:

AF XY:

0.00129

AC XY:

175

AN XY:

135450

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.0131

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000427

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00146

AC:

2051

AN:

1403732

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

1003

AN XY:

701952

show subpopulations

Gnomad4 AFR exome

AF:

0.000280

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.0135

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000495

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00135

Gnomad4 OTH exome

AF:

0.00247

GnomAD4 genome

AF:

0.00106

AC:

162

AN:

152288

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00290

Hom.:

Bravo

AF:

0.00106

Asia WGS

AF:

0.000289

AC:

AN:

3476

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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

-0.79

CADD

Benign

2.1

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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