16-31133898-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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 -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/exons	MANE	UniProt
PRSS8	NM_002773.5	c.104-510G>A		intron_variant		ENST00000317508.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS8	ENST00000317508.11	c.104-510G>A		intron_variant		1	NM_002773.5	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47863 AN: 151910 Hom.: 9520 Cov.: 32

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

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.477

Gnomad4 EAS exome AF: 0.913

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.430

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.427

GnomAD4 genome AF: 0.315 AC: 47862 AN: 152026 Hom.: 9520 Cov.: 32 AF XY: 0.318 AC XY: 23612 AN XY: 74300

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.891

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.377

Alfa AF: 0.366 Hom.: 11904

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
Dann	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs12597511; hg19: chr16-31145219;