rs8049043

Positions:

• chr16-31135418-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002773.5(PRSS8):​c.81G>C​(p.Gly27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,593,372 control chromosomes in the GnomAD database, including 3,099 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 0.084 (1653 hom., cov: 33)
  • Exomes 𝑓: 0.013 (1446 hom.)
• Consequence: PRSS8 NM_002773.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-1.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS8	NM_002773.5	c.81G>C	p.Gly27=	synonymous_variant	1/6	ENST00000317508.11	NP_002764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS8	ENST00000317508.11	c.81G>C	p.Gly27=	synonymous_variant	1/6	1	NM_002773.5	ENSP00000319730	P1

Frequencies

GnomAD3 genomes AF: 0.0836 AC: 12716 AN: 152152 Hom.: 1646 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0358

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00585

Gnomad OTH AF: 0.0703

GnomAD3 exomes AF: 0.0226 AC: 4862 AN: 215074 Hom.: 503 AF XY: 0.0178 AC XY: 2070 AN XY: 116188

Gnomad AFR exome AF: 0.283

Gnomad AMR exome AF: 0.0185

Gnomad ASJ exome AF: 0.00656

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00637

Gnomad FIN exome AF: 0.000512

Gnomad NFE exome AF: 0.00553

Gnomad OTH exome AF: 0.0164

GnomAD4 exome AF: 0.0126 AC: 18225 AN: 1441102 Hom.: 1446 Cov.: 31 AF XY: 0.0117 AC XY: 8369 AN XY: 714864

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.0205

Gnomad4 ASJ exome AF: 0.00668

Gnomad4 EAS exome AF: 0.0000781

Gnomad4 SAS exome AF: 0.00609

Gnomad4 FIN exome AF: 0.000617

Gnomad4 NFE exome AF: 0.00517

Gnomad4 OTH exome AF: 0.0237

GnomAD4 genome AF: 0.0837 AC: 12745 AN: 152270 Hom.: 1653 Cov.: 33 AF XY: 0.0804 AC XY: 5986 AN XY: 74456

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.0357

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00538

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00585

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0266 Hom.: 125

Bravo AF: 0.0950

Asia WGS AF: 0.0400 AC: 141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.61
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

Other links and lift over

dbSNP: rs8049043; hg19: chr16-31146739;