rs139591041

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_024747.6(HPS6):c.99A>G(p.Arg33Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,543,738 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 31 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 26 hom. )

Consequence

HPS6
NM_024747.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.201

Publications

2 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=-0.57).

BP6

Variant 10-102065573-A-G is Benign according to our data. Variant chr10-102065573-A-G is described in ClinVar as Benign. ClinVar VariationId is 163680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.201 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0106 (1608/152058) while in subpopulation AFR AF = 0.0327 (1357/41482). AF 95% confidence interval is 0.0313. There are 31 homozygotes in GnomAd4. There are 781 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS6	NM_024747.6 link	c.99A>G	p.Arg33Arg	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.99A>G	p.Arg33Arg	synonymous_variant	Exon 1 of 1	6	NM_024747.6	ENSP00000299238.5		Q86YV9

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1607

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.000912

Gnomad OTH

AF:

0.00956

GnomAD2 exomes

AF:

0.00234

AC:

349

AN:

149186

AF XY:

0.00192

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.00456

Gnomad ASJ exome

AF:

0.000659

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00101

Gnomad OTH exome

AF:

0.00508

GnomAD4 exome

AF:

0.00183

AC:

2552

AN:

1391680

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1147

AN XY:

689820

show subpopulations

African (AFR)

AF:

0.0334

AC:

971

AN:

29108

American (AMR)

AF:

0.00557

AC:

209

AN:

37550

Ashkenazi Jewish (ASJ)

AF:

0.000490

AC:

AN:

24470

East Asian (EAS)

AF:

0.00

AC:

AN:

34814

South Asian (SAS)

AF:

0.0000755

AC:

AN:

79510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34774

Middle Eastern (MID)

AF:

0.00600

AC:

AN:

4330

European-Non Finnish (NFE)

AF:

0.000951

AC:

1036

AN:

1089232

Other (OTH)

AF:

0.00504

AC:

292

AN:

57892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

151

303

454

606

757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.0106

AC:

1608

AN:

152058

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

781

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0327

AC:

1357

AN:

41482

American (AMR)

AF:

0.0105

AC:

161

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000913

AC:

AN:

67942

Other (OTH)

AF:

0.00946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

168

252

336

420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00184

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.00232

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jun 15, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

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

Arg33Arg in exon 1 of HPS6: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 0.8% (20/2358) of Afri can American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS; dbSNP rs139591041). -

not provided

Benign:2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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 13, 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

-0.57

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

0.20

PromoterAI

-0.0042

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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