Genetic Variant PRSS33:p.Gly164Val (chr16-2785398-C-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_152891.3(PRSS33):c.491G>T(p.Gly164Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRSS33
NM_152891.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13

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: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.993

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS33	NM_152891.3 link	c.491G>T	p.Gly164Val	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.491G>T	p.Gly164Val	missense_variant	Exon 5 of 7		NM_152891.3	ENSP00000507560.1		Q8NF86

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1281004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

624706

African (AFR)

AF:

0.00

AC:

AN:

26224

American (AMR)

AF:

0.00

AC:

AN:

17930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18318

East Asian (EAS)

AF:

0.00

AC:

AN:

32370

South Asian (SAS)

AF:

0.00

AC:

AN:

62586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1036340

Other (OTH)

AF:

0.00

AC:

AN:

53014

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.491G>T (p.G164V) alteration is located in exon 4 (coding exon 4) of the PRSS33 gene. This alteration results from a G to T substitution at nucleotide position 491, causing the glycine (G) at amino acid position 164 to be replaced by a valine (V). 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

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.52

BayesDel_noAF

Pathogenic

0.50

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

D;D;D

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

.;D;D

M_CAP

Pathogenic

0.87

MetaRNN

Pathogenic

0.99

D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

4.5

H;H;.

PhyloP100

2.1

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-8.9

D;.;.

REVEL

Pathogenic

0.94

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

D;D;.

Vest4

0.85

MutPred

0.92

Gain of glycosylation at T163 (P = 0.1131);Gain of glycosylation at T163 (P = 0.1131);.;

MVP

0.92

MPC

1.3

ClinPred

1.0

GERP RS

4.7

Varity_R

0.88

gMVP

0.91

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over