chr16-2855783-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022119.4(PRSS22):​c.350G>A​(p.Arg117Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000551 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

PRSS22
NM_022119.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.512
Variant links:
Genes affected
PRSS22 (HGNC:14368): (serine protease 22) This gene encodes a member of the trypsin family of serine proteases. The enzyme is expressed in the airways in a developmentally regulated manner. The gene is part of a cluster of serine protease genes on chromosome 16. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11102921).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRSS22NM_022119.4 linkc.350G>A p.Arg117Gln missense_variant Exon 4 of 6 ENST00000161006.8 NP_071402.1 Q9GZN4
PRSS22XM_047434451.1 linkc.137G>A p.Arg46Gln missense_variant Exon 2 of 4 XP_047290407.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRSS22ENST00000161006.8 linkc.350G>A p.Arg117Gln missense_variant Exon 4 of 6 1 NM_022119.4 ENSP00000161006.3 Q9GZN4

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152130
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000479
AC:
12
AN:
250550
Hom.:
0
AF XY:
0.0000443
AC XY:
6
AN XY:
135516
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.0000995
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000442
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000540
AC:
79
AN:
1461752
Hom.:
0
Cov.:
32
AF XY:
0.0000468
AC XY:
34
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000612
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152130
Hom.:
0
Cov.:
31
AF XY:
0.0000673
AC XY:
5
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000617
Hom.:
0
Bravo
AF:
0.000136
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000455
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 06, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.350G>A (p.R117Q) alteration is located in exon 4 (coding exon 4) of the PRSS22 gene. This alteration results from a G to A substitution at nucleotide position 350, causing the arginine (R) at amino acid position 117 to be replaced by a glutamine (Q). 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
0.083
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.044
N
M_CAP
Benign
0.052
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.50
T
MutationAssessor
Benign
0.23
N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
0.020
N
REVEL
Benign
0.27
Sift
Benign
0.53
T
Sift4G
Benign
0.63
T
Polyphen
0.81
P
Vest4
0.13
MVP
0.82
MPC
0.77
ClinPred
0.14
T
GERP RS
3.7
Varity_R
0.049
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs143806431; hg19: chr16-2905784; API