Variant 9-33750847-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000429677.8(PRSS3):c.14G>C(p.Gly5Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,380,954 control chromosomes in the GnomAD database, including 15,434 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3715 hom., cov: 31)

Exomes 𝑓: 0.13 ( 11719 hom. )

Consequence

PRSS3
ENST00000429677.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.00

Variant links:

Genes affected

PRSS3 (HGNC:9486): (serine protease 3) This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is expressed in the brain and pancreas and is resistant to common trypsin inhibitors. It is active on peptide linkages involving the carboxyl group of lysine or arginine. This gene is localized to the locus of T cell receptor beta variable orphans on chromosome 9. Four transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2010]

PRSS3 links:

UBE2R2-AS1 (HGNC:49911): (UBE2R2 antisense RNA 1)

UBE2R2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6629696E-4).

BP6

Variant 9-33750847-G-C is Benign according to our data. Variant chr9-33750847-G-C is described in ClinVar as [Benign]. Clinvar id is 1259461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2R2-AS1	NR_170204.1 linkuse as main transcript	n.559-12431C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2R2-AS1	ENST00000705030.1 linkuse as main transcript	n.644-12431C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28474

AN:

151856

Hom.:

3699

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0360

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.173

GnomAD3 exomes

AF:

0.110

AC:

1902

AN:

17262

Hom.:

169

AF XY:

0.115

AC XY:

1095

AN XY:

9542

show subpopulations

Gnomad AFR exome

AF:

0.359

Gnomad AMR exome

AF:

0.0812

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.0285

Gnomad SAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.0848

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.130

AC:

159395

AN:

1228978

Hom.:

11719

Cov.:

AF XY:

0.130

AC XY:

76996

AN XY:

592968

show subpopulations

Gnomad4 AFR exome

AF:

0.377

Gnomad4 AMR exome

AF:

0.0968

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.0338

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.188

AC:

28537

AN:

151976

Hom.:

3715

Cov.:

AF XY:

0.187

AC XY:

13887

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.366

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.0361

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.171

Alfa

AF:

0.161

Hom.:

318

Bravo

AF:

0.193

TwinsUK

AF:

0.133

AC:

495

ALSPAC

AF:

0.130

AC:

502

ExAC

AF:

0.0405

AC:

1141

Asia WGS

AF:

0.109

AC:

377

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.013

DANN

Benign

0.41

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.27

MetaRNN

Benign

0.00017

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P

PROVEAN

Benign

1.1

REVEL

Benign

0.090

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.036

ClinPred

0.0055

GERP RS

-3.9

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over