rs2689230

chr3-149150374-C-Gchr3-149150374-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032383.5(HPS3):c.1164-225C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,976 control chromosomes in the GnomAD database, including 3,662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3662 hom., cov: 31)
• Consequence: HPS3 NM_032383.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.202

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-149150374-C-G is Benign according to our data. Variant chr3-149150374-C-G is described in ClinVar as [Benign]. Clinvar id is 1241960.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPS3	NM_032383.5	c.1164-225C>G		intron_variant		ENST00000296051.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPS3	ENST00000296051.7	c.1164-225C>G		intron_variant		1	NM_032383.5	P1
HPS3	ENST00000460120.5	c.669-225C>G		intron_variant		2
HPS3	ENST00000462030.5	n.1763-225C>G		intron_variant, non_coding_transcript_variant		2
HPS3	ENST00000486530.1	n.1197-225C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32217 AN: 151858 Hom.: 3665 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.212 AC: 32235 AN: 151976 Hom.: 3662 Cov.: 31 AF XY: 0.214 AC XY: 15889 AN XY: 74258

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.185

Alfa AF: 0.133 Hom.: 274

Bravo AF: 0.199

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.83
Dann	Benign	0.59

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: rs2689230; hg19: chr3-148868161;