16-31132437-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002773.5(PRSS8):​c.697G>A​(p.Ala233Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

PRSS8
NM_002773.5 missense

Scores

2
13
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.424
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRSS8NM_002773.5 linkc.697G>A p.Ala233Thr missense_variant Exon 5 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.697G>A p.Ala233Thr missense_variant Exon 5 of 6 1 NM_002773.5 ENSP00000319730.6 Q16651-1
PRSS8ENST00000568261.5 linkc.535G>A p.Ala179Thr missense_variant Exon 5 of 6 2 ENSP00000457750.1 Q16651-2
PRSS8ENST00000567531.5 linkc.*2G>A downstream_gene_variant 3 ENSP00000457673.1 H3BUJ8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248752
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134924
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461382
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
726906
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113
ExAC
AF:
0.00000826
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 30, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.697G>A (p.A233T) alteration is located in exon 5 (coding exon 5) of the PRSS8 gene. This alteration results from a G to A substitution at nucleotide position 697, causing the alanine (A) at amino acid position 233 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.46
BayesDel_addAF
Uncertain
0.056
T
BayesDel_noAF
Uncertain
-0.070
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.58
D;.
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.79
D;D
MetaSVM
Uncertain
0.51
D
MutationAssessor
Benign
0.52
N;.
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-2.2
N;N
REVEL
Uncertain
0.60
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.060
T;T
Polyphen
1.0
D;.
Vest4
0.57
MutPred
0.80
Gain of ubiquitination at K231 (P = 0.143);.;
MVP
0.93
MPC
0.92
ClinPred
0.75
D
GERP RS
4.5
Varity_R
0.68
gMVP
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs768072440; hg19: chr16-31143758; COSMIC: COSV54899080; COSMIC: COSV54899080; API