Genetic Variant NM_002773.5:c.925C>A (chr16-31132116-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.925C>A(p.His309Asn) 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. H309Y) 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: -0.643

Publications

1 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:

ENSG00000261385 (HGNC:):

ENSG00000261385 links:

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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=0.08292955).

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.925C>A	p.His309Asn	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.925C>A	p.His309Asn	missense	Exon 6 of 6	ENSP00000319730.6	Q16651-1
PRSS8	ENST00000964168.1		c.901C>A	p.His301Asn	missense	Exon 6 of 6	ENSP00000634227.1
PRSS8	ENST00000568261.5	TSL:2	c.763C>A	p.His255Asn	missense	Exon 6 of 6	ENSP00000457750.1	Q16651-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246298

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

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

0.066

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.47

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.13

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.32

M_CAP

Benign

0.043

MetaRNN

Benign

0.083

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.0

PhyloP100

-0.64

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.21

REVEL

Benign

0.15

Sift

Benign

0.27

Sift4G

Benign

0.47

Polyphen

0.0010

Vest4

0.11

MutPred

0.24

Gain of disorder (P = 0.0775)

MVP

0.65

MPC

0.31

ClinPred

0.071

GERP RS

-7.3

Varity_R

0.071

gMVP

0.53

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

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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