rs750042020

Variant summary

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

The NM_152891.3(PRSS33):​c.830G>T​(p.Arg277Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R277H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PRSS33
NM_152891.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.96

Publications

0 publications found
Variant links:
Genes affected
PRSS33 (HGNC:30405): (serine protease 33) Enables serine-type endopeptidase activity. Involved in protein kinase C signaling and proteolysis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.080444455).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRSS33NM_152891.3 linkc.830G>T p.Arg277Leu missense_variant Exon 7 of 7 ENST00000682474.1 NP_690851.2 Q8NF86

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRSS33ENST00000682474.1 linkc.830G>T p.Arg277Leu missense_variant Exon 7 of 7 NM_152891.3 ENSP00000507560.1 Q8NF86
PRSS33ENST00000293851.9 linkc.830G>T p.Arg277Leu missense_variant Exon 6 of 6 1 ENSP00000293851.5 Q8NF86
PRSS33ENST00000570702.5 linkc.830G>T p.Arg277Leu missense_variant Exon 7 of 7 1 ENSP00000458369.1 Q8NF86
PRSS33ENST00000576886.5 linkc.*409G>T 3_prime_UTR_variant Exon 4 of 4 1 ENSP00000459051.1 I3L1S0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.92e-7
AC:
1
AN:
1444890
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
717264
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32996
American (AMR)
AF:
0.00
AC:
0
AN:
43270
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25746
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38838
South Asian (SAS)
AF:
0.00
AC:
0
AN:
83704
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51376
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5708
European-Non Finnish (NFE)
AF:
9.06e-7
AC:
1
AN:
1103534
Other (OTH)
AF:
0.00
AC:
0
AN:
59718
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

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
0.60
DANN
Benign
0.91
DEOGEN2
Benign
0.00072
T;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.036
N
LIST_S2
Benign
0.38
.;T
M_CAP
Benign
0.078
D
MetaRNN
Benign
0.080
T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.40
N;N
PhyloP100
-2.0
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.88
N;.
REVEL
Benign
0.24
Sift
Benign
0.13
T;.
Sift4G
Benign
0.39
T;T
Polyphen
0.0020
B;B
Vest4
0.17
MutPred
0.48
Loss of MoRF binding (P = 0.016);Loss of MoRF binding (P = 0.016);
MVP
0.12
MPC
0.50
ClinPred
0.075
T
GERP RS
-5.4
Varity_R
0.043
gMVP
0.55
Mutation Taster
=98/2
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: rs750042020; hg19: chr16-2834658; API