Variant chr10-102065990-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024747.6(HPS6):c.516G>A(p.Gly172Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0966 in 1,600,686 control chromosomes in the GnomAD database, including 8,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 604 hom., cov: 33)

Exomes 𝑓: 0.098 ( 7751 hom. )

Consequence

HPS6
NM_024747.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0430

Variant links:

Genes affected

HPS6 (HGNC:18817): (HPS6 biogenesis of lysosomal organelles complex 2 subunit 3) This intronless 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 5 protein. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 6. [provided by RefSeq, Jul 2008]

HPS6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 10-102065990-G-A is Benign according to our data. Variant chr10-102065990-G-A is described in ClinVar as [Benign]. Clinvar id is 163683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.043 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS6	NM_024747.6 link	c.516G>A	p.Gly172Gly	synonymous_variant	1/1	ENST00000299238.7	NP_079023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPS6	ENST00000299238.7 link	c.516G>A	p.Gly172Gly	synonymous_variant	1/1	6	NM_024747.6	ENSP00000299238.5		Q86YV9

Frequencies

GnomAD3 genomes

AF:

0.0787

AC:

11970

AN:

152128

Hom.:

604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0184

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0768

Gnomad ASJ

AF:

0.0726

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0775

GnomAD3 exomes

AF:

0.0867

AC:

20265

AN:

233706

Hom.:

1071

AF XY:

0.0849

AC XY:

10924

AN XY:

128668

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.0635

Gnomad ASJ exome

AF:

0.0778

Gnomad EAS exome

AF:

0.157

Gnomad SAS exome

AF:

0.0238

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0866

GnomAD4 exome

AF:

0.0985

AC:

142623

AN:

1448440

Hom.:

7751

Cov.:

AF XY:

0.0964

AC XY:

69531

AN XY:

720942

show subpopulations

Gnomad4 AFR exome

AF:

0.0155

Gnomad4 AMR exome

AF:

0.0647

Gnomad4 ASJ exome

AF:

0.0743

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.0241

Gnomad4 FIN exome

AF:

0.117

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.0946

GnomAD4 genome

AF:

0.0786

AC:

11966

AN:

152246

Hom.:

604

Cov.:

AF XY:

0.0777

AC XY:

5786

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.0767

Gnomad4 ASJ

AF:

0.0726

Gnomad4 EAS

AF:

0.150

Gnomad4 SAS

AF:

0.0294

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.0786

Alfa

AF:

0.0971

Hom.:

726

Bravo

AF:

0.0729

Asia WGS

AF:

0.0690

AC:

239

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 15, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Gly172Gly in exon 1 of HPS6: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 9.9% (847/8590) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs3737243). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 24, 2018	- -

Hermansky-Pudlak syndrome 6

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.6

DANN

Benign

0.81

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