Variant chr9-33798019-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_002771.4(PRSS3):c.391A>G(p.Thr131Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.70 ( 27687 hom., cov: 38)

Exomes 𝑓: 0.73 ( 316286 hom. )

Failed GnomAD Quality Control

Consequence

PRSS3
NM_002771.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.108

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1308639E-6).

BP6

Variant 9-33798019-A-G is Benign according to our data. Variant chr9-33798019-A-G is described in ClinVar as [Benign]. Clinvar id is 2786908.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS3	NM_002771.4 linkuse as main transcript	c.391A>G	p.Thr131Ala	missense_variant	3/5	ENST00000379405.4	NP_002762.3
UBE2R2-AS1	NR_170204.1 linkuse as main transcript	n.558+349T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS3	ENST00000379405.4 linkuse as main transcript	c.391A>G	p.Thr131Ala	missense_variant	3/5	1	NM_002771.4	ENSP00000368715	P1	P35030-3
UBE2R2-AS1	ENST00000705030.1 linkuse as main transcript	n.425+349T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

95619

AN:

135884

Hom.:

27684

Cov.:

FAILED QC

Gnomad AFR

AF:

0.633

Gnomad AMI

AF:

0.730

Gnomad AMR

AF:

0.712

Gnomad ASJ

AF:

0.718

Gnomad EAS

AF:

0.890

Gnomad SAS

AF:

0.835

Gnomad FIN

AF:

0.710

Gnomad MID

AF:

0.771

Gnomad NFE

AF:

0.718

Gnomad OTH

AF:

0.704

GnomAD3 exomes

AF:

0.960

AC:

233319

AN:

243014

Hom.:

111817

AF XY:

0.962

AC XY:

126489

AN XY:

131442

show subpopulations

Gnomad AFR exome

AF:

0.902

Gnomad AMR exome

AF:

0.955

Gnomad ASJ exome

AF:

0.962

Gnomad EAS exome

AF:

0.990

Gnomad SAS exome

AF:

0.986

Gnomad FIN exome

AF:

0.960

Gnomad NFE exome

AF:

0.958

Gnomad OTH exome

AF:

0.964

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.726

AC:

1015042

AN:

1397528

Hom.:

316286

Cov.:

100

AF XY:

0.730

AC XY:

508137

AN XY:

696372

show subpopulations

Gnomad4 AFR exome

AF:

0.644

Gnomad4 AMR exome

AF:

0.739

Gnomad4 ASJ exome

AF:

0.750

Gnomad4 EAS exome

AF:

0.919

Gnomad4 SAS exome

AF:

0.849

Gnomad4 FIN exome

AF:

0.756

Gnomad4 NFE exome

AF:

0.708

Gnomad4 OTH exome

AF:

0.753

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.704

AC:

95682

AN:

136004

Hom.:

27687

Cov.:

AF XY:

0.703

AC XY:

46813

AN XY:

66578

show subpopulations

Gnomad4 AFR

AF:

0.633

Gnomad4 AMR

AF:

0.712

Gnomad4 ASJ

AF:

0.718

Gnomad4 EAS

AF:

0.890

Gnomad4 SAS

AF:

0.835

Gnomad4 FIN

AF:

0.710

Gnomad4 NFE

AF:

0.718

Gnomad4 OTH

AF:

0.708

Alfa

AF:

0.756

Hom.:

6490

ExAC

AF:

0.910

AC:

110526

Asia WGS

AF:

0.999

AC:

3475

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.27

CADD

Benign

0.66

DANN

Benign

0.58

DEOGEN2

Benign

0.16

.;T;.;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.0091

T;T;T;T;T

MetaRNN

Benign

0.0000011

T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.47

.;N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.91

N;N;N;N;N

REVEL

Uncertain

0.39

Sift

Benign

0.43

T;T;T;T;T

Sift4G

Benign

0.44

T;T;T;T;T

Polyphen

0.0

B;B;.;.;B

Vest4

0.070

MPC

0.24

ClinPred

0.00030

GERP RS

-4.3

Varity_R

0.026

gMVP

0.17

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.

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