rs3737243

Variant names:

• chr10-102065990-G-A
• rs3737243
• NM_024747.6:c.516G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0430
• Publications: 11 publications found

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, Labcorp Genetics (formerly Invitae), G2P
• Hermansky-Pudlak syndrome without pulmonary fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024747.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS6	NM_024747.6	MANE Select	c.516G>A	p.Gly172Gly	synonymous	Exon 1 of 1	NP_079023.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS6	ENST00000299238.7	TSL:6 MANE Select	c.516G>A	p.Gly172Gly	synonymous	Exon 1 of 1	ENSP00000299238.5	Q86YV9

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11970 AN: 152128 Hom.: 604 Cov.: 33

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

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.: 34 AF XY: 0.0964 AC XY: 69531 AN XY: 720942

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

GnomAD4 genome AF: 0.0786 AC: 11966 AN: 152246 Hom.: 604 Cov.: 33 AF XY: 0.0777 AC XY: 5786 AN XY: 74442

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: 8 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7351 AN: 67994

Other (OTH) AF: 0.0786 AC: 166 AN: 2112

Alfa AF: 0.0934 Hom.: 1013

Bravo AF: 0.0729

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Hermansky-Pudlak syndrome 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.6
DANN	Benign	0.81
PhyloP100		-0.043
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3737243; hg19: chr10-103825747; COSMIC: COSV54625134;