rs2689230

Variant names:

• chr3-149150374-C-G
• rs2689230
• NM_032383.5:c.1164-225C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-149150374-C-G
• chr3-149150374-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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, Labcorp Genetics (formerly Invitae), ClinGen
• Hermansky-Pudlak syndrome without pulmonary fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032383.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS3	NM_032383.5	MANE Select	c.1164-225C>G		intron	N/A	NP_115759.2
	HPS3	NM_001308258.2		c.669-225C>G		intron	N/A	NP_001295187.1	G5E9V4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPS3	ENST00000296051.7	TSL:1 MANE Select	c.1164-225C>G		intron	N/A	ENSP00000296051.2	Q969F9-1
	HPS3	ENST00000870872.1		c.1164-225C>G		intron	N/A	ENSP00000540931.1
	HPS3	ENST00000870871.1		c.1164-225C>G		intron	N/A	ENSP00000540930.1

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

African (AFR) AF: 0.158 AC: 6532 AN: 41446

American (AMR) AF: 0.172 AC: 2632 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1423 AN: 5154

South Asian (SAS) AF: 0.301 AC: 1449 AN: 4814

European-Finnish (FIN) AF: 0.284 AC: 2992 AN: 10536

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15998 AN: 67960

Other (OTH) AF: 0.185 AC: 390 AN: 2104

Alfa AF: 0.133 Hom.: 274

Bravo AF: 0.199

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.83
DANN	Benign	0.59
PhyloP100		-0.20
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: rs2689230; hg19: chr3-148868161;