16-31135476-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002773.5(PRSS8):c.23G>A(p.Gly8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,578,322 control chromosomes in the GnomAD database, including 32 homozygotes. 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 0.0040 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 27 hom. )

Consequence

PRSS8
NM_002773.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.536

Variant links:

Genes affected

PRSS8 (HGNC:9491): (serine protease 8) This gene encodes a member of the peptidase S1 or chymotrypsin family of serine proteases. The encoded preproprotein is proteolytically processed to generate light and heavy chains that associate via a disulfide bond to form the heterodimeric enzyme. This enzyme is highly expressed in prostate epithelia and is one of several proteolytic enzymes found in seminal fluid. This protease exhibits trypsin-like substrate specificity, cleaving protein substrates at the carboxyl terminus of lysine or arginine residues. The encoded protease partially mediates proteolytic activation of the epithelial sodium channel, a regulator of sodium balance, and may also play a role in epithelial barrier formation. [provided by RefSeq, Feb 2016]

PRSS8 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=0.0061965585).

BP6

Variant 16-31135476-C-T is Benign according to our data. Variant chr16-31135476-C-T is described in ClinVar as [Benign]. Clinvar id is 771199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00403 (5753/1425994) while in subpopulation MID AF= 0.0295 (169/5722). AF 95% confidence interval is 0.0259. There are 27 homozygotes in gnomad4_exome. There are 2958 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS8	NM_002773.5 link	c.23G>A	p.Gly8Glu	missense_variant	Exon 1 of 6	ENST00000317508.11	NP_002764.1	Q16651-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS8	ENST00000317508.11 link	c.23G>A	p.Gly8Glu	missense_variant	Exon 1 of 6	1	NM_002773.5	ENSP00000319730.6		Q16651-1

Frequencies

GnomAD3 genomes

AF:

0.00401

AC:

611

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00824

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00544

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00474

AC:

880

AN:

185814

Hom.:

AF XY:

0.00486

AC XY:

489

AN XY:

100592

show subpopulations

Gnomad AFR exome

AF:

0.000407

Gnomad AMR exome

AF:

0.00561

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00178

Gnomad FIN exome

AF:

0.000552

Gnomad NFE exome

AF:

0.00647

Gnomad OTH exome

AF:

0.0138

GnomAD4 exome

AF:

0.00403

AC:

5753

AN:

1425994

Hom.:

Cov.:

AF XY:

0.00419

AC XY:

2958

AN XY:

706298

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.00596

Gnomad4 ASJ exome

AF:

0.00884

Gnomad4 EAS exome

AF:

0.0000266

Gnomad4 SAS exome

AF:

0.00187

Gnomad4 FIN exome

AF:

0.000790

Gnomad4 NFE exome

AF:

0.00409

Gnomad4 OTH exome

AF:

0.00676

GnomAD4 genome

AF:

0.00400

AC:

610

AN:

152328

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000697

Gnomad4 AMR

AF:

0.00823

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00544

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00575

Hom.:

Bravo

AF:

0.00462

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000541

AC:

ESP6500EA

AF:

0.00590

AC:

ExAC

AF:

0.00359

AC:

427

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PRSS8: BS1, BS2 -

not specified

Benign:1

Jan 02, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

T;.;.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.42

T;T;T;T

MetaRNN

Benign

0.0062

T;T;T;T

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.7

L;L;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.11

T;T;.;.

Polyphen

0.0060

B;.;.;.

Vest4

0.20

MVP

0.76

MPC

0.37

ClinPred

0.044

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.16

gMVP

0.78

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