Genetic Variant PRSS33:p.Glu87Lys (chr16-2785630-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_152891.3(PRSS33):c.259G>A(p.Glu87Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000534 in 1,498,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

PRSS33
NM_152891.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0650

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11520478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS33	NM_152891.3 link	c.259G>A	p.Glu87Lys	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.259G>A	p.Glu87Lys	missense_variant	Exon 5 of 7		NM_152891.3	ENSP00000507560.1		Q8NF86

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000102

AC:

AN:

98200

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000192

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.43e-7

AC:

AN:

1346432

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

662312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29788

American (AMR)

AF:

0.00

AC:

AN:

29456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22606

East Asian (EAS)

AF:

0.00

AC:

AN:

34742

South Asian (SAS)

AF:

0.00

AC:

AN:

74866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3882

European-Non Finnish (NFE)

AF:

9.41e-7

AC:

AN:

1062722

Other (OTH)

AF:

0.00

AC:

AN:

55936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 27, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.259G>A (p.E87K) alteration is located in exon 4 (coding exon 4) of the PRSS33 gene. This alteration results from a G to A substitution at nucleotide position 259, causing the glutamic acid (E) at amino acid position 87 to be replaced by a lysine (K). 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

0.33

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.45

.;T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.32

N;N;.

PhyloP100

-0.065

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.4

N;.;.

REVEL

Uncertain

0.37

Sift

Benign

0.43

T;.;.

Sift4G

Benign

0.57

T;T;.

Polyphen

0.0070

B;B;.

Vest4

0.23

MutPred

0.46

Gain of MoRF binding (P = 0.0042);Gain of MoRF binding (P = 0.0042);.;

MVP

0.27

MPC

0.51

ClinPred

0.018

GERP RS

1.4

Varity_R

0.047

gMVP

0.63

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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16-2785630-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over