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
• Publications: 5 publications found

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS8	NM_002773.5	MANE Select	c.81G>C	p.Gly27Gly	synonymous	Exon 1 of 6	NP_002764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS8	ENST00000317508.11	TSL:1 MANE Select	c.81G>C	p.Gly27Gly	synonymous	Exon 1 of 6	ENSP00000319730.6
	PRSS8	ENST00000567833.1	TSL:1	n.286G>C		non_coding_transcript_exon	Exon 1 of 2
	PRSS8	ENST00000568261.5	TSL:2	c.81G>C	p.Gly27Gly	synonymous	Exon 1 of 6	ENSP00000457750.1

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

African (AFR) AF: 0.286 AC: 9379 AN: 32806

American (AMR) AF: 0.0205 AC: 847 AN: 41244

Ashkenazi Jewish (ASJ) AF: 0.00668 AC: 172 AN: 25744

East Asian (EAS) AF: 0.0000781 AC: 3 AN: 38412

South Asian (SAS) AF: 0.00609 AC: 506 AN: 83082

European-Finnish (FIN) AF: 0.000617 AC: 32 AN: 51848

Middle Eastern (MID) AF: 0.0303 AC: 174 AN: 5744

European-Non Finnish (NFE) AF: 0.00517 AC: 5696 AN: 1102506

Other (OTH) 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

African (AFR) AF: 0.278 AC: 11550 AN: 41528

American (AMR) AF: 0.0357 AC: 546 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.00538 AC: 26 AN: 4830

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10624

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00585 AC: 398 AN: 68016

Other (OTH) AF: 0.0695 AC: 147 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.61
DANN	Benign	0.66
PhyloP100		-1.2
PromoterAI		0.036	Neutral
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

Other links and lift over

dbSNP: rs8049043; hg19: chr16-31146739;