11-86807686-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007173.6(PRSS23):​c.43C>T​(p.Leu15Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PRSS23
NM_007173.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

Publications

0 publications found
Variant links:
Genes affected
PRSS23 (HGNC:14370): (serine protease 23) This gene encodes a conserved member of the trypsin family of serine proteases. Mouse studies found a decrease of mRNA levels of this gene after ovulation was induced. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13541552).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRSS23NM_007173.6 linkc.43C>T p.Leu15Phe missense_variant Exon 2 of 2 ENST00000280258.6 NP_009104.3 O95084-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRSS23ENST00000280258.6 linkc.43C>T p.Leu15Phe missense_variant Exon 2 of 2 1 NM_007173.6 ENSP00000280258.4 O95084-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461688
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727156
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44706
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26104
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86230
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111898
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 08, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.43C>T (p.L15F) alteration is located in exon 2 (coding exon 1) of the PRSS23 gene. This alteration results from a C to T substitution at nucleotide position 43, causing the leucine (L) at amino acid position 15 to be replaced by a phenylalanine (F). 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
Benign
0.063
BayesDel_addAF
Benign
-0.028
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.035
T;T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.47
N
LIST_S2
Benign
0.44
T;T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
.;M
PhyloP100
1.4
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.039
Sift
Benign
0.098
T;T
Sift4G
Benign
0.23
T;T
Polyphen
0.44
.;B
Vest4
0.10
MutPred
0.24
Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP
0.39
MPC
0.20
ClinPred
0.30
T
GERP RS
4.9
Varity_R
0.058
gMVP
0.34
Mutation Taster
=78/22
polymorphism

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

Other links and lift over

dbSNP: rs751626725; hg19: chr11-86518728; API