rs16861552

Variant names:

• chr3-149151844-T-C
• rs16861552
• NM_032383.5:c.1245+1164T>C

Variant summary

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

The NM_032383.5(HPS3):​c.1245+1164T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,128 control chromosomes in the GnomAD database, including 5,690 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 0.26 (5690 hom., cov: 32)
• Consequence: HPS3 NM_032383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS3	NM_032383.5	c.1245+1164T>C		intron_variant	Intron 6 of 16	ENST00000296051.7	NP_115759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS3	ENST00000296051.7	c.1245+1164T>C		intron_variant	Intron 6 of 16	1	NM_032383.5	ENSP00000296051.2
HPS3	ENST00000460120.5	c.750+1164T>C		intron_variant	Intron 5 of 15	2		ENSP00000418230.1
HPS3	ENST00000462030.5	n.1844+1164T>C		intron_variant	Intron 6 of 6	2
HPS3	ENST00000486530.1	n.1278+1164T>C		intron_variant	Intron 6 of 6	5

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39860 AN: 152010 Hom.: 5667 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.262 AC: 39927 AN: 152128 Hom.: 5690 Cov.: 32 AF XY: 0.264 AC XY: 19620 AN XY: 74356

African (AFR) AF: 0.384 AC: 15927 AN: 41488

American (AMR) AF: 0.247 AC: 3778 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3472

East Asian (EAS) AF: 0.158 AC: 818 AN: 5178

South Asian (SAS) AF: 0.236 AC: 1139 AN: 4818

European-Finnish (FIN) AF: 0.273 AC: 2883 AN: 10558

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14032 AN: 68014

Other (OTH) AF: 0.241 AC: 508 AN: 2112

Alfa AF: 0.233 Hom.: 1626

Bravo AF: 0.267

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.54
PhyloP100		-0.28
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: rs16861552; hg19: chr3-148869631; COSMIC: COSV107355061;