rs2689232

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_032383.5(HPS3):​c.1164-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,606,278 control chromosomes in the GnomAD database, including 41,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.18 ( 3072 hom., cov: 31)
Exomes 𝑓: 0.22 ( 38449 hom. )

Consequence

HPS3
NM_032383.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.541
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4
This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 3-149150574-C-T is Benign according to our data. Variant chr3-149150574-C-T is described in ClinVar as [Benign]. Clinvar id is 262023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HPS3NM_032383.5 linkuse as main transcriptc.1164-25C>T intron_variant ENST00000296051.7 NP_115759.2 Q969F9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HPS3ENST00000296051.7 linkuse as main transcriptc.1164-25C>T intron_variant 1 NM_032383.5 ENSP00000296051.2 Q969F9-1
HPS3ENST00000460120.5 linkuse as main transcriptc.669-25C>T intron_variant 2 ENSP00000418230.1 G5E9V4
HPS3ENST00000462030.5 linkuse as main transcriptn.1763-25C>T intron_variant 2
HPS3ENST00000486530.1 linkuse as main transcriptn.1197-25C>T intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.181
AC:
27466
AN:
152034
Hom.:
3075
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0657
Gnomad AMI
AF:
0.309
Gnomad AMR
AF:
0.156
Gnomad ASJ
AF:
0.118
Gnomad EAS
AF:
0.275
Gnomad SAS
AF:
0.300
Gnomad FIN
AF:
0.282
Gnomad MID
AF:
0.105
Gnomad NFE
AF:
0.228
Gnomad OTH
AF:
0.149
GnomAD3 exomes
AF:
0.212
AC:
53155
AN:
250742
Hom.:
6242
AF XY:
0.220
AC XY:
29854
AN XY:
135508
show subpopulations
Gnomad AFR exome
AF:
0.0612
Gnomad AMR exome
AF:
0.136
Gnomad ASJ exome
AF:
0.122
Gnomad EAS exome
AF:
0.278
Gnomad SAS exome
AF:
0.292
Gnomad FIN exome
AF:
0.267
Gnomad NFE exome
AF:
0.224
Gnomad OTH exome
AF:
0.183
GnomAD4 exome
AF:
0.224
AC:
326012
AN:
1454126
Hom.:
38449
Cov.:
30
AF XY:
0.227
AC XY:
164363
AN XY:
723866
show subpopulations
Gnomad4 AFR exome
AF:
0.0577
Gnomad4 AMR exome
AF:
0.137
Gnomad4 ASJ exome
AF:
0.123
Gnomad4 EAS exome
AF:
0.269
Gnomad4 SAS exome
AF:
0.292
Gnomad4 FIN exome
AF:
0.264
Gnomad4 NFE exome
AF:
0.228
Gnomad4 OTH exome
AF:
0.210
GnomAD4 genome
AF:
0.181
AC:
27468
AN:
152152
Hom.:
3072
Cov.:
31
AF XY:
0.185
AC XY:
13720
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0657
Gnomad4 AMR
AF:
0.156
Gnomad4 ASJ
AF:
0.118
Gnomad4 EAS
AF:
0.276
Gnomad4 SAS
AF:
0.300
Gnomad4 FIN
AF:
0.282
Gnomad4 NFE
AF:
0.228
Gnomad4 OTH
AF:
0.149
Alfa
AF:
0.198
Hom.:
632
Bravo
AF:
0.163
Asia WGS
AF:
0.256
AC:
892
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxJul 09, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Hermansky-Pudlak syndrome 3 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
CADD
Benign
17
DANN
Benign
0.77
BranchPoint Hunter
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2689232; hg19: chr3-148868361; COSMIC: COSV56052875; API