Genetic Variant PRSS8:p.Leu288Ile (chr16-31132179-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002773.5(PRSS8):c.862C>A(p.Leu288Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L288F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

PRSS8
NM_002773.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.104

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07052204).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002773.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS8	NM_002773.5	MANE Select	c.862C>A	p.Leu288Ile	missense	Exon 6 of 6	NP_002764.1	Q16651-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRSS8	ENST00000317508.11	TSL:1 MANE Select	c.862C>A	p.Leu288Ile	missense	Exon 6 of 6	ENSP00000319730.6	Q16651-1
PRSS8	ENST00000964168.1		c.838C>A	p.Leu280Ile	missense	Exon 6 of 6	ENSP00000634227.1
PRSS8	ENST00000568261.5	TSL:2	c.700C>A	p.Leu234Ile	missense	Exon 6 of 6	ENSP00000457750.1	Q16651-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248748

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.17

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.56

M_CAP

Benign

0.047

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.5

PhyloP100

0.10

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.27

REVEL

Benign

0.061

Sift

Benign

0.15

Sift4G

Benign

0.35

Polyphen

0.021

Vest4

0.11

MutPred

0.32

Gain of catalytic residue at P290 (P = 0.03)

MVP

0.69

MPC

0.31

ClinPred

0.046

GERP RS

2.3

Varity_R

0.18

gMVP

0.72

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over