3-149130286-C-G

Position:

• chr3-149130286-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032383.5(HPS3):​c.217+346C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 367,022 control chromosomes in the GnomAD database, including 1,625 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 0.077 (556 hom., cov: 32)
  • Exomes 𝑓: 0.087 (1069 hom.)
• Consequence: HPS3 NM_032383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS3	NM_032383.5	c.217+346C>G		intron_variant		ENST00000296051.7	NP_115759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPS3	ENST00000296051.7	c.217+346C>G		intron_variant		1	NM_032383.5	ENSP00000296051.2

Frequencies

GnomAD3 genomes AF: 0.0769 AC: 11689 AN: 152032 Hom.: 554 Cov.: 32

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0741

Gnomad ASJ AF: 0.0871

Gnomad EAS AF: 0.00810

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0818

GnomAD4 exome AF: 0.0870 AC: 18694 AN: 214872 Hom.: 1069 Cov.: 0 AF XY: 0.0901 AC XY: 10103 AN XY: 112166

Gnomad4 AFR exome AF: 0.0443

Gnomad4 AMR exome AF: 0.0633

Gnomad4 ASJ exome AF: 0.0831

Gnomad4 EAS exome AF: 0.00621

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0397

Gnomad4 NFE exome AF: 0.0965

Gnomad4 OTH exome AF: 0.0824

GnomAD4 genome AF: 0.0769 AC: 11695 AN: 152150 Hom.: 556 Cov.: 32 AF XY: 0.0736 AC XY: 5476 AN XY: 74370

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.0740

Gnomad4 ASJ AF: 0.0871

Gnomad4 EAS AF: 0.00812

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0352

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0862

Alfa AF: 0.0340 Hom.: 21

Bravo AF: 0.0751

Asia WGS AF: 0.0830 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.39

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: rs7643410; hg19: chr3-148848073;