rs8049043

Variant names:

• chr16-31135418-C-G
• rs8049043
• NM_002773.5:c.81G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-31135418-C-G
• chr16-31135418-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002773.5(PRSS8):​c.81G>C​(p.Gly27Gly) 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRSS8	NM_002773.5	c.81G>C	p.Gly27Gly	synonymous_variant	Exon 1 of 6	ENST00000317508.11	NP_002764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS8	ENST00000317508.11	c.81G>C	p.Gly27Gly	synonymous_variant	Exon 1 of 6	1	NM_002773.5	ENSP00000319730.6

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

GnomAD2 exomes AF: 0.0226 AC: 4862 AN: 215074 AF XY: 0.0178

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 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 AC: 9379 AN: 32806

Gnomad4 AMR exome AF: 0.0205 AC: 847 AN: 41244

Gnomad4 ASJ exome AF: 0.00668 AC: 172 AN: 25744

Gnomad4 EAS exome AF: 0.0000781 AC: 3 AN: 38412

Gnomad4 SAS exome AF: 0.00609 AC: 506 AN: 83082

Gnomad4 FIN exome AF: 0.000617 AC: 32 AN: 51848

Gnomad4 NFE exome AF: 0.00517 AC: 5696 AN: 1102506

Gnomad4 Remaining exome AF: 0.0237 AC: 1416 AN: 59716

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 AC: 0.278126 AN: 0.278126

Gnomad4 AMR AF: 0.0357 AC: 0.0356816 AN: 0.0356816

Gnomad4 ASJ AF: 0.00519 AC: 0.00518732 AN: 0.00518732

Gnomad4 EAS AF: 0.000386 AC: 0.0003861 AN: 0.0003861

Gnomad4 SAS AF: 0.00538 AC: 0.00538302 AN: 0.00538302

Gnomad4 FIN AF: 0.000377 AC: 0.000376506 AN: 0.000376506

Gnomad4 NFE AF: 0.00585 AC: 0.00585156 AN: 0.00585156

Gnomad4 OTH AF: 0.0695 AC: 0.0695364 AN: 0.0695364

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
Mutation Taster		=100/0	polymorphism (auto)

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;