Genetic Variant PRSS33:p.Val183Glu (chr16-2785138-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152891.3(PRSS33):c.548T>A(p.Val183Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000389 in 1,543,100 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

PRSS33
NM_152891.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31552032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS33	NM_152891.3 link	c.548T>A	p.Val183Glu	missense_variant	Exon 6 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.548T>A	p.Val183Glu	missense_variant	Exon 6 of 7		NM_152891.3	ENSP00000507560.1		Q8NF86

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151866

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000139

AC:

AN:

144212

AF XY:

0.0000128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000359

AC:

AN:

1391234

Hom.:

Cov.:

AF XY:

0.00000583

AC XY:

AN XY:

686656

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31730

American (AMR)

AF:

0.0000280

AC:

AN:

35758

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25154

East Asian (EAS)

AF:

0.00

AC:

AN:

35846

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79276

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1079450

Other (OTH)

AF:

0.00

AC:

AN:

57982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151866

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41326

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 26, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.548T>A (p.V183E) alteration is located in exon 5 (coding exon 5) of the PRSS33 gene. This alteration results from a T to A substitution at nucleotide position 548, causing the valine (V) at amino acid position 183 to be replaced by a glutamic acid (E). 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

0.62

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.040

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.019

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.30

M_CAP

Pathogenic

0.39

MetaRNN

Benign

0.32

PhyloP100

1.1

Sift4G

Benign

0.36

Vest4

0.18

MVP

0.74

ClinPred

0.92

GERP RS

3.3

Varity_R

0.65

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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16-2785138-A-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