rs16861552

Positions:

• chr3-149151844-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HPS3	NM_032383.5	c.1245+1164T>C		intron_variant		ENST00000296051.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPS3	ENST00000296051.7	c.1245+1164T>C		intron_variant		1	NM_032383.5	P1
HPS3	ENST00000460120.5	c.750+1164T>C		intron_variant		2
HPS3	ENST00000462030.5	n.1844+1164T>C		intron_variant, non_coding_transcript_variant		2
HPS3	ENST00000486530.1	n.1278+1164T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.241

Alfa AF: 0.237 Hom.: 1070

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs16861552; hg19: chr3-148869631;