10-102067980-T-G

Variant names:

• chr10-102067980-T-G
• rs3816
• NM_024747.6:c.*178T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024747.6(HPS6):​c.*178T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 707,136 control chromosomes in the GnomAD database, including 19,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3647 hom., cov: 32)
  • Exomes 𝑓: 0.22 (16024 hom.)
• Consequence: HPS6 NM_024747.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.514
• Publications: 19 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, G2P, Labcorp Genetics (formerly Invitae)
• Hermansky-Pudlak syndrome without pulmonary fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-102067980-T-G is Benign according to our data. Variant chr10-102067980-T-G is described in ClinVar as Benign. ClinVar VariationId is 261761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS6	NM_024747.6	MANE Select	c.*178T>G		3_prime_UTR	Exon 1 of 1	NP_079023.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS6	ENST00000299238.7	TSL:6 MANE Select	c.*178T>G		3_prime_UTR	Exon 1 of 1	ENSP00000299238.5

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31418 AN: 152044 Hom.: 3639 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.218 AC: 120848 AN: 554974 Hom.: 16024 Cov.: 6 AF XY: 0.221 AC XY: 65413 AN XY: 296478

African (AFR) AF: 0.206 AC: 3068 AN: 14902

American (AMR) AF: 0.224 AC: 6683 AN: 29824

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 4894 AN: 18080

East Asian (EAS) AF: 0.576 AC: 18290 AN: 31770

South Asian (SAS) AF: 0.271 AC: 16037 AN: 59122

European-Finnish (FIN) AF: 0.129 AC: 6045 AN: 46840

Middle Eastern (MID) AF: 0.250 AC: 785 AN: 3136

European-Non Finnish (NFE) AF: 0.182 AC: 58663 AN: 321558

Other (OTH) AF: 0.215 AC: 6383 AN: 29742

GnomAD4 genome AF: 0.207 AC: 31448 AN: 152162 Hom.: 3647 Cov.: 32 AF XY: 0.209 AC XY: 15534 AN XY: 74404

African (AFR) AF: 0.208 AC: 8627 AN: 41526

American (AMR) AF: 0.220 AC: 3358 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 949 AN: 3466

East Asian (EAS) AF: 0.521 AC: 2688 AN: 5162

South Asian (SAS) AF: 0.298 AC: 1438 AN: 4824

European-Finnish (FIN) AF: 0.120 AC: 1273 AN: 10600

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12456 AN: 67988

Other (OTH) AF: 0.222 AC: 469 AN: 2108

Alfa AF: 0.197 Hom.: 12560

Bravo AF: 0.216

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hermansky-Pudlak syndrome 6 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.51
PhyloP100		0.51
Mutation Taster		=100/0	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: rs3816; hg19: chr10-103827737; COSMIC: COSV54626429;