chr16-2856115-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022119.4(PRSS22):​c.248G>A​(p.Arg83His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

PRSS22
NM_022119.4 missense

Scores

5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.181
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRSS22NM_022119.4 linkc.248G>A p.Arg83His missense_variant Exon 3 of 6 ENST00000161006.8 NP_071402.1 Q9GZN4
PRSS22XM_047434451.1 linkc.-196G>A 5_prime_UTR_variant Exon 2 of 4 XP_047290407.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRSS22ENST00000161006.8 linkc.248G>A p.Arg83His missense_variant Exon 3 of 6 1 NM_022119.4 ENSP00000161006.3 Q9GZN4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251256
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135800
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1461746
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.248G>A (p.R83H) alteration is located in exon 3 (coding exon 3) of the PRSS22 gene. This alteration results from a G to A substitution at nucleotide position 248, causing the arginine (R) at amino acid position 83 to be replaced by a histidine (H). 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
0.092
BayesDel_addAF
Uncertain
0.056
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
T
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.085
FATHMM_MKL
Benign
0.17
N
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.23
T
MetaSVM
Uncertain
-0.11
T
MutationAssessor
Benign
1.8
L
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-2.1
N
REVEL
Uncertain
0.41
Sift
Benign
0.16
T
Sift4G
Benign
0.12
T
Polyphen
0.027
B
Vest4
0.23
MutPred
0.60
Loss of stability (P = 0.0351);
MVP
0.84
MPC
0.49
ClinPred
0.18
T
GERP RS
4.9
Varity_R
0.056
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.24
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.24
Position offset: -4

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: rs759759990; hg19: chr16-2906116; API