3-149156465-G-T

Variant names:

• chr3-149156465-G-T
• rs6785780
• NM_032383.5:c.1510-885G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032383.5(HPS3):​c.1510-885G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,896 control chromosomes in the GnomAD database, including 15,230 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15230 hom., cov: 31)
• Consequence: HPS3 NM_032383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 2 publications found

Genes affected

HPS3 (HGNC:15597): (HPS3 biogenesis of lysosomal organelles complex 2 subunit 1) This gene encodes a protein containing a potential clathrin-binding motif, consensus dileucine signals, and tyrosine-based sorting signals for targeting to vesicles of lysosomal lineage. The encoded protein may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 3. [provided by RefSeq, Apr 2015]

HPS3 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032383.5. 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
	HPS3	NM_032383.5	MANE Select	c.1510-885G>T		intron	N/A	NP_115759.2
	HPS3	NM_001308258.2		c.1015-885G>T		intron	N/A	NP_001295187.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS3	ENST00000296051.7	TSL:1 MANE Select	c.1510-885G>T		intron	N/A	ENSP00000296051.2
	HPS3	ENST00000460120.5	TSL:2	c.1015-885G>T		intron	N/A	ENSP00000418230.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67700 AN: 151780 Hom.: 15216 Cov.: 31

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.423

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.446 AC: 67748 AN: 151896 Hom.: 15230 Cov.: 31 AF XY: 0.445 AC XY: 33030 AN XY: 74238

African (AFR) AF: 0.465 AC: 19276 AN: 41410

American (AMR) AF: 0.358 AC: 5470 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1347 AN: 3472

East Asian (EAS) AF: 0.369 AC: 1903 AN: 5164

South Asian (SAS) AF: 0.512 AC: 2467 AN: 4822

European-Finnish (FIN) AF: 0.474 AC: 4989 AN: 10518

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30953 AN: 67928

Other (OTH) AF: 0.425 AC: 895 AN: 2106

Alfa AF: 0.440 Hom.: 40743

Bravo AF: 0.434

Asia WGS AF: 0.436 AC: 1519 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.7
DANN	Benign	0.57
PhyloP100		0.16
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: rs6785780; hg19: chr3-148874252;