Genetic Variant PRSS57:p.Gly30Glu (chr19-694958-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_001308209.2(PRSS57):c.89G>A(p.Gly30Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,392,742 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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. G30V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000015 ( 1 hom. )

Consequence

PRSS57
NM_001308209.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0770

Publications

2 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: 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=0.16058454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS57	NM_001308209.2 link	c.89G>A	p.Gly30Glu	missense_variant	Exon 2 of 5	ENST00000329267.9	NP_001295138.2	B7ZMF6
PRSS57	NM_214710.5 link	c.92G>A	p.Gly31Glu	missense_variant	Exon 2 of 5		NP_999875.2	Q6UWY2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS57	ENST00000329267.9 link	c.89G>A	p.Gly30Glu	missense_variant	Exon 2 of 5	1	NM_001308209.2	ENSP00000327386.6		A0A0A0MR61
PRSS57	ENST00000613411.4 link	c.92G>A	p.Gly31Glu	missense_variant	Exon 2 of 5	1		ENSP00000482358.1		Q6UWY2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000584

AC:

AN:

171216

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:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1392742

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

688398

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30746

American (AMR)

AF:

0.0000300

AC:

AN:

33346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22236

East Asian (EAS)

AF:

0.00

AC:

AN:

37420

South Asian (SAS)

AF:

0.00

AC:

AN:

77906

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5290

European-Non Finnish (NFE)

AF:

0.0000176

AC:

AN:

1079298

Other (OTH)

AF:

0.0000175

AC:

AN:

57160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.048

T;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.48

T;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.38

MutationAssessor

Benign

0.0

N;.

PhyloP100

0.077

PrimateAI

Benign

0.42

REVEL

Benign

0.23

Sift4G

Uncertain

0.012

D;D

Polyphen

0.60

P;.

Vest4

0.42

MutPred

0.43

Gain of catalytic residue at G31 (P = 0.0531);.;

MVP

0.12

MPC

0.059

ClinPred

0.29

GERP RS

-4.4

PromoterAI

0.071

Neutral

(source)

Varity_R

0.13

gMVP

0.40

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over