Genetic Variant PRSS57:p.Arg126Gln (chr19-691859-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001308209.2(PRSS57):c.377G>A(p.Arg126Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 1,329,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

PRSS57
NM_001308209.2 missense, splice_region

Scores

Splicing: ADA: 0.0006454

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.572

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:

Genome browser will be placed here

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=0.15389594).

BP6

Variant 19-691859-C-T is Benign according to our data. Variant chr19-691859-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3219948.Status of the report is criteria_provided_single_submitter, 1 stars.

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.377G>A	p.Arg126Gln	missense splice_region	Exon 3 of 5	NP_001295138.2	A0A0A0MR61
	PRSS57	NM_214710.5		c.380G>A	p.Arg127Gln	missense splice_region	Exon 3 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.377G>A	p.Arg126Gln	missense splice_region	Exon 3 of 5	ENSP00000327386.6	A0A0A0MR61
	PRSS57	ENST00000613411.4	TSL:1	c.380G>A	p.Arg127Gln	missense splice_region	Exon 3 of 5	ENSP00000482358.1	Q6UWY2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152090

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:

0.000193

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:

0.0000163

AC:

AN:

122746

AF XY:

0.0000152

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:

0.0000304

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000849

AC:

AN:

1177576

Hom.:

Cov.:

AF XY:

0.00000883

AC XY:

AN XY:

566340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25030

American (AMR)

AF:

0.00

AC:

AN:

17696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15620

East Asian (EAS)

AF:

0.00

AC:

AN:

30602

South Asian (SAS)

AF:

0.00

AC:

AN:

32498

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4668

European-Non Finnish (NFE)

AF:

0.0000104

AC:

AN:

962188

Other (OTH)

AF:

0.00

AC:

AN:

47114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

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

AF:

0.0000132

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

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:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000838

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.1

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.63

M_CAP

Benign

0.061

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.31

PhyloP100

-0.57

PrimateAI

Benign

0.29

REVEL

Benign

0.26

Sift4G

Benign

0.31

Polyphen

0.017

Vest4

0.079

MVP

0.19

MPC

0.016

ClinPred

0.049

GERP RS

-0.28

Varity_R

0.23

gMVP

0.29

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00065

dbscSNV1_RF

Benign

0.20

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