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GeneBe

11-86807695-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007173.6(PRSS23):c.52G>A(p.Val18Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000034 ( 0 hom. )

Consequence

PRSS23
NM_007173.6 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.481
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05356267).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRSS23NM_007173.6 linkuse as main transcriptc.52G>A p.Val18Ile missense_variant 2/2 ENST00000280258.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRSS23ENST00000280258.6 linkuse as main transcriptc.52G>A p.Val18Ile missense_variant 2/21 NM_007173.6 P1O95084-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461812
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 07, 2022The c.52G>A (p.V18I) alteration is located in exon 2 (coding exon 1) of the PRSS23 gene. This alteration results from a G to A substitution at nucleotide position 52, causing the valine (V) at amino acid position 18 to be replaced by an isoleucine (I). 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
0.071
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
Cadd
Benign
0.52
Dann
Benign
0.33
DEOGEN2
Benign
0.012
T;T
Eigen
Benign
-0.96
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.56
T;T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.054
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.27
N;N
REVEL
Benign
0.11
Sift
Benign
0.54
T;T
Sift4G
Benign
0.75
T;T
Polyphen
0.0
.;B
Vest4
0.039
MutPred
0.40
Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);
MVP
0.18
MPC
0.15
ClinPred
0.044
T
GERP RS
1.2
Varity_R
0.018
gMVP
0.077

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-86518737; API