20-45175881-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002638.4(PI3):ā€‹c.100A>Cā€‹(p.Thr34Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,613,876 control chromosomes in the GnomAD database, including 26,291 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.16 ( 2026 hom., cov: 32)
Exomes š‘“: 0.18 ( 24265 hom. )

Consequence

PI3
NM_002638.4 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.40
Variant links:
Genes affected
PI3 (HGNC:8947): (peptidase inhibitor 3) This gene encodes an elastase-specific inhibitor that functions as an antimicrobial peptide against Gram-positive and Gram-negative bacteria, and fungal pathogens. The protein contains a WAP-type four-disulfide core (WFDC) domain, and is thus a member of the WFDC domain family. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the centromeric cluster. Expression of this gene is upgulated by bacterial lipopolysaccharides and cytokines. [provided by RefSeq, Oct 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.001419872).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PI3NM_002638.4 linkuse as main transcriptc.100A>C p.Thr34Pro missense_variant 2/3 ENST00000243924.4 NP_002629.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PI3ENST00000243924.4 linkuse as main transcriptc.100A>C p.Thr34Pro missense_variant 2/31 NM_002638.4 ENSP00000243924 P1

Frequencies

GnomAD3 genomes
AF:
0.157
AC:
23921
AN:
152048
Hom.:
2021
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.124
Gnomad AMI
AF:
0.316
Gnomad AMR
AF:
0.135
Gnomad ASJ
AF:
0.205
Gnomad EAS
AF:
0.0326
Gnomad SAS
AF:
0.143
Gnomad FIN
AF:
0.193
Gnomad MID
AF:
0.231
Gnomad NFE
AF:
0.182
Gnomad OTH
AF:
0.164
GnomAD3 exomes
AF:
0.155
AC:
39041
AN:
251378
Hom.:
3526
AF XY:
0.161
AC XY:
21846
AN XY:
135860
show subpopulations
Gnomad AFR exome
AF:
0.124
Gnomad AMR exome
AF:
0.0886
Gnomad ASJ exome
AF:
0.200
Gnomad EAS exome
AF:
0.0305
Gnomad SAS exome
AF:
0.164
Gnomad FIN exome
AF:
0.196
Gnomad NFE exome
AF:
0.186
Gnomad OTH exome
AF:
0.168
GnomAD4 exome
AF:
0.177
AC:
259373
AN:
1461710
Hom.:
24265
Cov.:
33
AF XY:
0.177
AC XY:
128810
AN XY:
727160
show subpopulations
Gnomad4 AFR exome
AF:
0.121
Gnomad4 AMR exome
AF:
0.0931
Gnomad4 ASJ exome
AF:
0.201
Gnomad4 EAS exome
AF:
0.0199
Gnomad4 SAS exome
AF:
0.167
Gnomad4 FIN exome
AF:
0.195
Gnomad4 NFE exome
AF:
0.188
Gnomad4 OTH exome
AF:
0.169
GnomAD4 genome
AF:
0.157
AC:
23960
AN:
152166
Hom.:
2026
Cov.:
32
AF XY:
0.158
AC XY:
11740
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.124
Gnomad4 AMR
AF:
0.135
Gnomad4 ASJ
AF:
0.205
Gnomad4 EAS
AF:
0.0324
Gnomad4 SAS
AF:
0.144
Gnomad4 FIN
AF:
0.193
Gnomad4 NFE
AF:
0.182
Gnomad4 OTH
AF:
0.168
Alfa
AF:
0.179
Hom.:
6596
Bravo
AF:
0.151
TwinsUK
AF:
0.193
AC:
714
ALSPAC
AF:
0.202
AC:
777
ESP6500AA
AF:
0.127
AC:
560
ESP6500EA
AF:
0.184
AC:
1581
ExAC
AF:
0.156
AC:
18922
Asia WGS
AF:
0.0930
AC:
322
AN:
3478
EpiCase
AF:
0.183
EpiControl
AF:
0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.81
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.018
DANN
Benign
0.58
DEOGEN2
Benign
0.047
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.43
T
MetaRNN
Benign
0.0014
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.73
N
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.28
N
REVEL
Benign
0.030
Sift
Benign
0.46
T
Sift4G
Benign
0.36
T
Polyphen
0.018
B
Vest4
0.033
MPC
0.22
ClinPred
0.0070
T
GERP RS
-5.1
Varity_R
0.13
gMVP
0.20

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: rs2664581; hg19: chr20-43804522; COSMIC: COSV54782855; API