rs16861514

Variant names:

• chr3-149139464-C-T
• rs16861514
• NM_032383.5:c.218-540C>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.218-540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,096 control chromosomes in the GnomAD database, including 2,174 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 0.17 (2174 hom., cov: 32)
• Consequence: HPS3 NM_032383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS3	NM_032383.5	c.218-540C>T		intron_variant	Intron 1 of 16	ENST00000296051.7	NP_115759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS3	ENST00000296051.7	c.218-540C>T		intron_variant	Intron 1 of 16	1	NM_032383.5	ENSP00000296051.2
HPS3	ENST00000460120.5	c.218-1553C>T		intron_variant	Intron 1 of 15	2		ENSP00000418230.1
HPS3	ENST00000462030.5	n.817-540C>T		intron_variant	Intron 1 of 6	2
HPS3	ENST00000486530.1	n.251-540C>T		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25199 AN: 151978 Hom.: 2170 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.166 AC: 25236 AN: 152096 Hom.: 2174 Cov.: 32 AF XY: 0.169 AC XY: 12557 AN XY: 74328

African (AFR) AF: 0.194 AC: 8061 AN: 41470

American (AMR) AF: 0.192 AC: 2937 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3470

East Asian (EAS) AF: 0.157 AC: 811 AN: 5176

South Asian (SAS) AF: 0.132 AC: 635 AN: 4824

European-Finnish (FIN) AF: 0.231 AC: 2445 AN: 10564

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9442 AN: 67998

Other (OTH) AF: 0.157 AC: 331 AN: 2112

Alfa AF: 0.149 Hom.: 7407

Bravo AF: 0.167

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.9
DANN	Benign	0.67
PhyloP100		0.29
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: rs16861514; hg19: chr3-148857251;