Variant 19-846169-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002777.4(PRTN3):c.392G>A(p.Ser131Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000589 in 1,479,614 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 1 hom. )

Consequence

PRTN3
NM_002777.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0660

Variant links:

Genes affected

PRTN3 (HGNC:9495): (proteinase 3) Enables enzyme binding activity; serine-type endopeptidase activity; and signaling receptor binding activity. Involved in several processes, including mature conventional dendritic cell differentiation; membrane protein ectodomain proteolysis; and neutrophil extravasation. Located in azurophil granule lumen; cytosol; and plasma membrane raft. Colocalizes with plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PRTN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022724122).

BP6

Variant 19-846169-G-A is Benign according to our data. Variant chr19-846169-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2402472.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRTN3	NM_002777.4 linkuse as main transcript	c.392G>A	p.Ser131Asn	missense_variant	4/5	ENST00000234347.10	NP_002768.3
PRTN3	XM_011528136.2 linkuse as main transcript	c.392G>A	p.Ser131Asn	missense_variant	4/5		XP_011526438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRTN3	ENST00000234347.10 linkuse as main transcript	c.392G>A	p.Ser131Asn	missense_variant	4/5	1	NM_002777.4	ENSP00000234347	P1
PRTN3	ENST00000544537.2 linkuse as main transcript	c.269G>A	p.Ser90Asn	missense_variant	3/4	1		ENSP00000475174

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000515

AC:

AN:

108754

Hom.:

AF XY:

0.000559

AC XY:

AN XY:

58988

show subpopulations

Gnomad AFR exome

AF:

0.000303

Gnomad AMR exome

AF:

0.000427

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000453

Gnomad NFE exome

AF:

0.000788

Gnomad OTH exome

AF:

0.00266

GnomAD4 exome

AF:

0.000602

AC:

799

AN:

1327424

Hom.:

Cov.:

AF XY:

0.000607

AC XY:

394

AN XY:

649014

show subpopulations

Gnomad4 AFR exome

AF:

0.000105

Gnomad4 AMR exome

AF:

0.000484

Gnomad4 ASJ exome

AF:

0.0000453

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000514

Gnomad4 NFE exome

AF:

0.000687

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.000473

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000644

Hom.:

Bravo

AF:

0.000468

ESP6500AA

AF:

0.000234

AC:

ESP6500EA

AF:

0.000477

AC:

ExAC

AF:

0.000380

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.21

DANN

Benign

0.17

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.29

T;T

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.42

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

2.5

N;.

REVEL

Benign

0.071

Sift

Benign

1.0

T;.

Sift4G

Benign

0.91

T;T

Polyphen

0.0

B;.

Vest4

0.11

MVP

0.45

MPC

0.20

ClinPred

0.0023

GERP RS

-1.1

Varity_R

0.13

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over