5-32786283-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001204375.2(NPR3):c.1564A>G(p.Asn522Asp) variant causes a missense change. The variant allele was found at a frequency of 0.21 in 1,581,236 control chromosomes in the GnomAD database, including 36,640 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2889 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33751 hom. )

Consequence

NPR3
NM_001204375.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.84

Variant links:

Genes affected

NPR3 (HGNC:7945): (natriuretic peptide receptor 3) This gene encodes one of three natriuretic peptide receptors. Natriutetic peptides are small peptides which regulate blood volume and pressure, pulmonary hypertension, and cardiac function as well as some metabolic and growth processes. The product of this gene encodes a natriuretic peptide receptor responsible for clearing circulating and extracellular natriuretic peptides through endocytosis of the receptor. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

NPR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012596548).

BP6

Variant 5-32786283-A-G is Benign according to our data. Variant chr5-32786283-A-G is described in ClinVar as [Benign]. Clinvar id is 1240702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2 link	c.1564A>G	p.Asn522Asp	missense_variant	Exon 8 of 8	ENST00000265074.13	NP_001191304.1	P17342-1A8K4A5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NPR3	ENST00000265074.13 link	c.1564A>G	p.Asn522Asp	missense_variant	Exon 8 of 8	1	NM_001204375.2	ENSP00000265074.8	P17342-1
NPR3	ENST00000415167.2 link	c.1561A>G	p.Asn521Asp	missense_variant	Exon 8 of 8	1		ENSP00000398028.2	P17342-2
NPR3	ENST00000434067.6 link	c.916A>G	p.Asn306Asp	missense_variant	Exon 8 of 8	5		ENSP00000388408.2	C9JK69
NPR3	ENST00000326958.5 link	c.913A>G	p.Asn305Asp	missense_variant	Exon 8 of 8	2		ENSP00000318340.2	P17342-3

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28373

AN:

152094

Hom.:

2891

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.165

GnomAD3 exomes

AF:

0.207

AC:

49130

AN:

237278

Hom.:

5394

AF XY:

0.210

AC XY:

26963

AN XY:

128260

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.205

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.203

Gnomad SAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.225

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.213

AC:

303721

AN:

1429024

Hom.:

33751

Cov.:

AF XY:

0.214

AC XY:

152270

AN XY:

711392

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.225

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.224

Gnomad4 NFE exome

AF:

0.214

Gnomad4 OTH exome

AF:

0.198

GnomAD4 genome

AF:

0.186

AC:

28380

AN:

152212

Hom.:

2889

Cov.:

AF XY:

0.191

AC XY:

14209

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.112

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.204

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.226

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.204

Hom.:

7837

Bravo

AF:

0.179

TwinsUK

AF:

0.219

AC:

812

ALSPAC

AF:

0.225

AC:

866

ESP6500AA

AF:

0.117

AC:

428

ESP6500EA

AF:

0.202

AC:

1649

ExAC

AF:

0.206

AC:

24861

Asia WGS

AF:

0.247

AC:

860

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24465655, 23493048) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

T;.;T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.067

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.62

T;T;T;T

MetaRNN

Benign

0.0013

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

.;.;L;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.57

N;.;N;N

REVEL

Benign

0.055

Sift

Benign

0.31

T;.;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.0010

.;.;B;.

Vest4

0.039

ClinPred

0.015

GERP RS

5.0

Varity_R

0.14

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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