Variant 16-31132091-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002773.5(PRSS8):c.950C>G(p.Ala317Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,609,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

PRSS8
NM_002773.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.186

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07326603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS8	NM_002773.5 linkuse as main transcript	c.950C>G	p.Ala317Gly	missense_variant	6/6	ENST00000317508.11	NP_002764.1	Q16651-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS8	ENST00000317508.11 linkuse as main transcript	c.950C>G	p.Ala317Gly	missense_variant	6/6	1	NM_002773.5	ENSP00000319730.6		Q16651-1
PRSS8	ENST00000568261.5 linkuse as main transcript	c.788C>G	p.Ala263Gly	missense_variant	6/6	2		ENSP00000457750.1		Q16651-2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000292

AC:

AN:

239364

Hom.:

AF XY:

0.0000461

AC XY:

AN XY:

130114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000649

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000364

AC:

AN:

1457172

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

724458

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000377

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000752

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.950C>G (p.A317G) alteration is located in exon 6 (coding exon 6) of the PRSS8 gene. This alteration results from a C to G substitution at nucleotide position 950, causing the alanine (A) at amino acid position 317 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.35

CADD

Benign

9.6

DANN

Benign

0.95

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.53

T;T

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.0

L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.12

Sift

Benign

0.078

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0020

B;.

Vest4

0.086

MVP

0.79

MPC

0.28

ClinPred

0.036

GERP RS

-0.45

Varity_R

0.13

gMVP

0.62

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