Genetic Variant PRSS57:p.Pro184Thr (chr19-687017-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001308209.2(PRSS57):c.550C>A(p.Pro184Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. P184S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PRSS57
NM_001308209.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.517

Publications

0 publications found

Variant links:

Genes affected

PRSS57 (HGNC:31397): (serine protease 57) This gene encodes an arginine-specific serine protease and member of the peptidase S1 family of proteins. The encoded protein may undergo proteolytic activation before storage in azurophil granules, in neutrophil cells of the immune system. Following neutrophil activation, the protease is released into the pericellular environment, where it may play a role in defense against microbial pathogens. [provided by RefSeq, Jul 2016]

PRSS57 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04045227).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308209.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS57	NM_001308209.2	MANE Select	c.550C>A	p.Pro184Thr	missense	Exon 4 of 5	NP_001295138.2	A0A0A0MR61
	PRSS57	NM_214710.5		c.553C>A	p.Pro185Thr	missense	Exon 4 of 5	NP_999875.2	Q6UWY2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS57	ENST00000329267.9	TSL:1 MANE Select	c.550C>A	p.Pro184Thr	missense	Exon 4 of 5	ENSP00000327386.6	A0A0A0MR61
	PRSS57	ENST00000613411.4	TSL:1	c.553C>A	p.Pro185Thr	missense	Exon 4 of 5	ENSP00000482358.1	Q6UWY2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111990

Other (OTH)

AF:

0.00

AC:

AN:

60394

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

Age Distribution

Exome Het

Variant carriers

<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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.8

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.080

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.50

M_CAP

Benign

0.028

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.83

MutationAssessor

Benign

-1.0

PhyloP100

0.52

PrimateAI

Benign

0.36

REVEL

Benign

0.18

Sift4G

Benign

0.27

Polyphen

0.0020

Vest4

0.093

MutPred

0.45

Gain of catalytic residue at P185 (P = 0.1386)

MVP

0.076

MPC

0.016

ClinPred

0.067

GERP RS

3.4

Varity_R

0.13

gMVP

0.56

Mutation Taster

=87/13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over