rs3737243

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

Hermansky-Pudlak syndrome 6
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
Hermansky-Pudlak syndrome without pulmonary fibrosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

HPS6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
HPS6	NM_024747.6 link	c.516G>A	p.Gly172Gly	synonymous_variant	Exon 1 of 1	ENST00000299238.7	NP_079023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS6	ENST00000299238.7 link	c.516G>A	p.Gly172Gly	synonymous_variant	Exon 1 of 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

GnomAD2 exomes

AF:

0.0867

AC:

20265

AN:

233706

AF XY:

0.0849

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 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

African (AFR)

AF:

0.0155

AC:

519

AN:

33468

American (AMR)

AF:

0.0647

AC:

2881

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.0743

AC:

1938

AN:

26086

East Asian (EAS)

AF:

0.112

AC:

4450

AN:

39668

South Asian (SAS)

AF:

0.0241

AC:

2080

AN:

86134

European-Finnish (FIN)

AF:

0.117

AC:

4804

AN:

40966

Middle Eastern (MID)

AF:

0.0320

AC:

184

AN:

5750

European-Non Finnish (NFE)

AF:

0.108

AC:

120064

AN:

1111562

Other (OTH)

AF:

0.0946

AC:

5703

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

8815

17630

26444

35259

44074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4296

8592

12888

17184

21480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0786

AC:

11966

AN:

152246

Hom.:

604

Cov.:

AF XY:

0.0777

AC XY:

5786

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0184

AC:

765

AN:

41574

American (AMR)

AF:

0.0767

AC:

1174

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0726

AC:

252

AN:

3470

East Asian (EAS)

AF:

0.150

AC:

777

AN:

5164

South Asian (SAS)

AF:

0.0294

AC:

142

AN:

4826

European-Finnish (FIN)

AF:

0.119

AC:

1263

AN:

10598

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7351

AN:

67994

Other (OTH)

AF:

0.0786

AC:

166

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

572

1143

1715

2286

2858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0934

Hom.:

1013

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

Apr 15, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 24, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hermansky-Pudlak syndrome 6

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.81

PhyloP100

-0.043

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over