chr16-31135425-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002773.5(PRSS8):​c.74G>A​(p.Arg25Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,594,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

PRSS8
NM_002773.5 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.65
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.028153628).
BP6
Variant 16-31135425-C-T is Benign according to our data. Variant chr16-31135425-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3784115.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRSS8NM_002773.5 linkc.74G>A p.Arg25Gln missense_variant Exon 1 of 6 ENST00000317508.11 NP_002764.1 Q16651-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRSS8ENST00000317508.11 linkc.74G>A p.Arg25Gln missense_variant Exon 1 of 6 1 NM_002773.5 ENSP00000319730.6 Q16651-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152218
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000462
AC:
10
AN:
216460
Hom.:
0
AF XY:
0.0000342
AC XY:
4
AN XY:
117038
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000650
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000644
Gnomad SAS exome
AF:
0.0000371
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000622
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000155
AC:
224
AN:
1442186
Hom.:
0
Cov.:
31
AF XY:
0.000151
AC XY:
108
AN XY:
715538
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000241
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000260
Gnomad4 SAS exome
AF:
0.0000361
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000195
Gnomad4 OTH exome
AF:
0.0000670
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152336
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000302
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000415
AC:
5

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 04, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
0.0030
DANN
Benign
0.72
DEOGEN2
Benign
0.18
T;.;.;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.47
T;T;T;T
M_CAP
Benign
0.082
D
MetaRNN
Benign
0.028
T;T;T;T
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
-0.20
N;N;.;.
PrimateAI
Benign
0.20
T
PROVEAN
Benign
0.98
N;N;N;N
REVEL
Uncertain
0.30
Sift
Benign
0.58
T;T;T;T
Sift4G
Benign
0.82
T;T;.;.
Polyphen
0.0050
B;.;.;.
Vest4
0.073
MutPred
0.44
Loss of solvent accessibility (P = 0.1077);Loss of solvent accessibility (P = 0.1077);Loss of solvent accessibility (P = 0.1077);Loss of solvent accessibility (P = 0.1077);
MVP
0.61
MPC
0.32
ClinPred
0.032
T
GERP RS
-8.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.022
gMVP
0.28

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs565045496; hg19: chr16-31146746; API