rs148529565

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

5 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: Benign. The variant received -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 VariationId 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. GnomAdExome4 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 GnomAdExome4. There are 2958 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

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.23G>A	p.Gly8Glu	missense	Exon 1 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.23G>A	p.Gly8Glu	missense	Exon 1 of 6	ENSP00000319730.6	Q16651-1
PRSS8	ENST00000567833.1	TSL:1	n.228G>A		non_coding_transcript_exon	Exon 1 of 2
PRSS8	ENST00000964168.1		c.23G>A	p.Gly8Glu	missense	Exon 1 of 6	ENSP00000634227.1

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

GnomAD2 exomes

AF:

0.00474

AC:

880

AN:

185814

AF XY:

0.00486

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 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

African (AFR)

AF:

0.00194

AC:

AN:

32480

American (AMR)

AF:

0.00596

AC:

232

AN:

38920

Ashkenazi Jewish (ASJ)

AF:

0.00884

AC:

224

AN:

25340

East Asian (EAS)

AF:

0.0000266

AC:

AN:

37616

South Asian (SAS)

AF:

0.00187

AC:

152

AN:

81408

European-Finnish (FIN)

AF:

0.000790

AC:

AN:

50658

Middle Eastern (MID)

AF:

0.0295

AC:

169

AN:

5722

European-Non Finnish (NFE)

AF:

0.00409

AC:

4473

AN:

1094800

Other (OTH)

AF:

0.00676

AC:

399

AN:

59050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

297

594

890

1187

1484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

134

268

402

536

670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00400

AC:

610

AN:

152328

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000697

AC:

AN:

41580

American (AMR)

AF:

0.00823

AC:

126

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00806

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00145

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00544

AC:

370

AN:

68014

Other (OTH)

AF:

0.00945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0062

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.7

PhyloP100

0.54

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Benign

0.11

Polyphen

0.0060

Vest4

0.20

MVP

0.76

MPC

0.37

ClinPred

0.044

GERP RS

1.3

PromoterAI

-0.036

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.16

gMVP

0.78

Mutation Taster

=99/1

polymorphism

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over