3-149151522-G-T

Variant names:

• chr3-149151522-G-T
• rs2689234
• NM_032383.5:c.1245+842G>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.1245+842G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 144,342 control chromosomes in the GnomAD database, including 22,724 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 0.56 (22724 hom., cov: 23)
• Consequence: HPS3 NM_032383.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS3	NM_032383.5	c.1245+842G>T		intron_variant	Intron 6 of 16	ENST00000296051.7	NP_115759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS3	ENST00000296051.7	c.1245+842G>T		intron_variant	Intron 6 of 16	1	NM_032383.5	ENSP00000296051.2
HPS3	ENST00000460120.5	c.750+842G>T		intron_variant	Intron 5 of 15	2		ENSP00000418230.1
HPS3	ENST00000462030.5	n.1844+842G>T		intron_variant	Intron 6 of 6	2
HPS3	ENST00000486530.1	n.1278+842G>T		intron_variant	Intron 6 of 6	5

Frequencies

GnomAD3 genomes AF: 0.562 AC: 81057 AN: 144236 Hom.: 22681 Cov.: 23

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.562 AC: 81150 AN: 144342 Hom.: 22724 Cov.: 23 AF XY: 0.569 AC XY: 39647 AN XY: 69714

African (AFR) AF: 0.668 AC: 26318 AN: 39388

American (AMR) AF: 0.506 AC: 6992 AN: 13818

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1397 AN: 3408

East Asian (EAS) AF: 0.466 AC: 2237 AN: 4796

South Asian (SAS) AF: 0.692 AC: 3185 AN: 4600

European-Finnish (FIN) AF: 0.627 AC: 5389 AN: 8596

Middle Eastern (MID) AF: 0.430 AC: 110 AN: 256

European-Non Finnish (NFE) AF: 0.512 AC: 34119 AN: 66590

Other (OTH) AF: 0.514 AC: 1024 AN: 1992

Alfa AF: 0.400 Hom.: 1092

Bravo AF: 0.540

Asia WGS AF: 0.587 AC: 2041 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.8
DANN	Benign	0.43
PhyloP100		0.17
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: rs2689234; hg19: chr3-148869309;