3-149134668-G-A

Position:

• chr3-149134668-G-A

Variant summary

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

The NM_032383.5(HPS3):​c.217+4728G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,968 control chromosomes in the GnomAD database, including 11,152 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 0.37 (11152 hom., cov: 32)
• Consequence: HPS3 NM_032383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPS3	NM_032383.5	c.217+4728G>A		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+4728G>A		intron_variant		1	NM_032383.5	ENSP00000296051	P1
HPS3	ENST00000460120.5	c.217+4728G>A		intron_variant		2		ENSP00000418230
HPS3	ENST00000462030.5	n.816+4215G>A		intron_variant, non_coding_transcript_variant		2
HPS3	ENST00000486530.1	n.250+4728G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55826 AN: 151850 Hom.: 11115 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.368 AC: 55917 AN: 151968 Hom.: 11152 Cov.: 32 AF XY: 0.364 AC XY: 27052 AN XY: 74288

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.365

Alfa AF: 0.309 Hom.: 9667

Bravo AF: 0.376

Asia WGS AF: 0.324 AC: 1131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.83
DANN	Benign	0.64

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: rs4681169; hg19: chr3-148852455;