Genetic Variant NM_002773.5:c.104-510G>A (chr16-31133898-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002773.5(PRSS8):c.104-510G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 163,972 control chromosomes in the GnomAD database, including 10,504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 9520 hom., cov: 32)

Exomes 𝑓: 0.37 ( 984 hom. )

Consequence

PRSS8
NM_002773.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

Publications

43 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS8	NM_002773.5 link	c.104-510G>A		intron_variant	Intron 2 of 5	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.104-510G>A		intron_variant	Intron 2 of 5	1	NM_002773.5	ENSP00000319730.6		Q16651-1

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47863

AN:

151910

Hom.:

9520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.435

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.891

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.378

GnomAD4 exome

AF:

0.371

AC:

4433

AN:

11946

Hom.:

984

AF XY:

0.369

AC XY:

2353

AN XY:

6384

show subpopulations

African (AFR)

AF:

0.136

AC:

AN:

272

American (AMR)

AF:

0.441

AC:

1108

AN:

2512

Ashkenazi Jewish (ASJ)

AF:

0.477

AC:

AN:

128

East Asian (EAS)

AF:

0.913

AC:

533

AN:

584

South Asian (SAS)

AF:

0.168

AC:

306

AN:

1818

European-Finnish (FIN)

AF:

0.430

AC:

AN:

142

Middle Eastern (MID)

AF:

0.450

AC:

AN:

European-Non Finnish (NFE)

AF:

0.353

AC:

2109

AN:

5980

Other (OTH)

AF:

0.427

AC:

209

AN:

490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

121

241

362

482

603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.315

AC:

47862

AN:

152026

Hom.:

9520

Cov.:

AF XY:

0.318

AC XY:

23612

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.121

AC:

5027

AN:

41490

American (AMR)

AF:

0.379

AC:

5775

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

1693

AN:

3468

East Asian (EAS)

AF:

0.891

AC:

4608

AN:

5170

South Asian (SAS)

AF:

0.163

AC:

787

AN:

4822

European-Finnish (FIN)

AF:

0.390

AC:

4115

AN:

10564

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.361

AC:

24512

AN:

67950

Other (OTH)

AF:

0.377

AC:

794

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1507

3013

4520

6026

7533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.359

Hom.:

14521

Bravo

AF:

0.319

Asia WGS

AF:

0.453

AC:

1579

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.18

(source)

DANN

Benign

0.48

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over