Genetic Variant PRSS33:p.Val162Leu (chr16-2785405-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_152891.3(PRSS33):c.484G>C(p.Val162Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,439,346 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

PRSS33
NM_152891.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62

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]

PRSS33 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS33	NM_152891.3 link	c.484G>C	p.Val162Leu	missense_variant	Exon 5 of 7	ENST00000682474.1	NP_690851.2	Q8NF86

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS33	ENST00000682474.1 link	c.484G>C	p.Val162Leu	missense_variant	Exon 5 of 7		NM_152891.3	ENSP00000507560.1		Q8NF86

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000588

AC:

AN:

51038

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000129

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000513

AC:

AN:

1287154

Hom.:

Cov.:

AF XY:

0.0000493

AC XY:

AN XY:

629068

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26354

American (AMR)

AF:

0.00

AC:

AN:

18434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18542

East Asian (EAS)

AF:

0.00

AC:

AN:

32390

South Asian (SAS)

AF:

0.0000157

AC:

AN:

63758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30682

Middle Eastern (MID)

AF:

0.000799

AC:

AN:

3756

European-Non Finnish (NFE)

AF:

0.0000567

AC:

AN:

1039950

Other (OTH)

AF:

0.0000563

AC:

AN:

53288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.000131

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000629

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 26, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.484G>C (p.V162L) alteration is located in exon 4 (coding exon 4) of the PRSS33 gene. This alteration results from a G to C substitution at nucleotide position 484, causing the valine (V) at amino acid position 162 to be replaced by a leucine (L). 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

Uncertain

0.56

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;T;D

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

.;D;T

M_CAP

Pathogenic

0.60

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Uncertain

0.29

MutationAssessor

Benign

1.1

L;L;.

PhyloP100

1.6

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.8

D;.;.

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

D;.;.

Sift4G

Uncertain

0.012

D;D;.

Polyphen

0.97

D;D;.

Vest4

0.39

MutPred

0.68

Gain of glycosylation at P159 (P = 0.1265);Gain of glycosylation at P159 (P = 0.1265);.;

MVP

0.70

MPC

1.1

ClinPred

0.60

GERP RS

4.7

Varity_R

0.63

gMVP

0.80

Mutation Taster

=84/16

polymorphism

(source)

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

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16-2785405-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over