Variant 19-847944-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002777.4(PRTN3):c.746G>A(p.Arg249His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00965 in 1,604,196 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0092 ( 24 hom., cov: 32)

Exomes 𝑓: 0.0097 ( 116 hom. )

Consequence

PRTN3
NM_002777.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.531

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003399998).

BP6

Variant 19-847944-G-A is Benign according to our data. Variant chr19-847944-G-A is described in ClinVar as [Benign]. Clinvar id is 3024761.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRTN3	NM_002777.4 linkuse as main transcript	c.746G>A	p.Arg249His	missense_variant	5/5	ENST00000234347.10	NP_002768.3
PRTN3	XM_011528136.2 linkuse as main transcript	c.*174G>A		3_prime_UTR_variant	5/5		XP_011526438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRTN3	ENST00000234347.10 linkuse as main transcript	c.746G>A	p.Arg249His	missense_variant	5/5	1	NM_002777.4	ENSP00000234347	P1
PRTN3	ENST00000544537.2 linkuse as main transcript	c.623G>A	p.Arg208His	missense_variant	4/4	1		ENSP00000475174

Frequencies

GnomAD3 genomes

AF:

0.00923

AC:

1405

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0472

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00979

AC:

2260

AN:

230946

Hom.:

AF XY:

0.00981

AC XY:

1232

AN XY:

125528

show subpopulations

Gnomad AFR exome

AF:

0.00188

Gnomad AMR exome

AF:

0.00229

Gnomad ASJ exome

AF:

0.00378

Gnomad EAS exome

AF:

0.000226

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.0459

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.00969

AC:

14069

AN:

1451838

Hom.:

116

Cov.:

AF XY:

0.00965

AC XY:

6965

AN XY:

721438

show subpopulations

Gnomad4 AFR exome

AF:

0.000839

Gnomad4 AMR exome

AF:

0.00246

Gnomad4 ASJ exome

AF:

0.00499

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.00170

Gnomad4 FIN exome

AF:

0.0454

Gnomad4 NFE exome

AF:

0.00979

Gnomad4 OTH exome

AF:

0.00786

GnomAD4 genome

AF:

0.00922

AC:

1405

AN:

152358

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

785

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00127

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0472

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00983

Hom.:

Bravo

AF:

0.00564

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0104

AC:

ExAC

AF:

0.00924

AC:

1116

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

PRTN3: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.53

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.4

N;.

REVEL

Benign

0.26

Sift

Uncertain

0.014

D;.

Sift4G

Uncertain

0.015

D;D

Polyphen

1.0

D;.

Vest4

0.19

MVP

0.91

MPC

0.70

ClinPred

0.025

GERP RS

1.6

Varity_R

0.11

gMVP

0.55

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

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