chr16-31135476-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002773.5(PRSS8):c.23G>A(p.Gly8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,578,322 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0040 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0040 ( 27 hom. )
Consequence
PRSS8
NM_002773.5 missense
NM_002773.5 missense
Scores
1
3
14
Clinical Significance
Conservation
PhyloP100: 0.536
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0061965585).
BP6
?
Variant 16-31135476-C-T is Benign according to our data. Variant chr16-31135476-C-T is described in ClinVar as [Benign]. Clinvar id is 771199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00403 (5753/1425994) while in subpopulation MID AF= 0.0295 (169/5722). AF 95% confidence interval is 0.0259. There are 27 homozygotes in gnomad4_exome. There are 2958 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRSS8 | NM_002773.5 | c.23G>A | p.Gly8Glu | missense_variant | 1/6 | ENST00000317508.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRSS8 | ENST00000317508.11 | c.23G>A | p.Gly8Glu | missense_variant | 1/6 | 1 | NM_002773.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00401 AC: 611AN: 152210Hom.: 5 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00474 AC: 880AN: 185814Hom.: 4 AF XY: 0.00486 AC XY: 489AN XY: 100592
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GnomAD4 exome AF: 0.00403 AC: 5753AN: 1425994Hom.: 27 Cov.: 31 AF XY: 0.00419 AC XY: 2958AN XY: 706298
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GnomAD4 genome ? AF: 0.00400 AC: 610AN: 152328Hom.: 5 Cov.: 33 AF XY: 0.00396 AC XY: 295AN XY: 74480
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Asia WGS
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | PRSS8: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 05, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital | Jan 02, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;.;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Benign
T;T;.;.
Polyphen
B;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at