5-32786283-A-G

Variant names:

• chr5-32786283-A-G
• rs2270915
• NM_001204375.2:c.1564A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. N522N) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.19 (2889 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33751 hom.)
• Consequence: NPR3 NM_001204375.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.84
• Publications: 36 publications found

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 Gene-Disease associations (from GenCC):

• Boudin-Mortier syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204375.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR3	NM_001204375.2	MANE Select	c.1564A>G	p.Asn522Asp	missense	Exon 8 of 8	NP_001191304.1
	NPR3	NM_000908.4		c.1561A>G	p.Asn521Asp	missense	Exon 8 of 8	NP_000899.1
	NPR3	NM_001363652.2		c.916A>G	p.Asn306Asp	missense	Exon 8 of 8	NP_001350581.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR3	ENST00000265074.13	TSL:1 MANE Select	c.1564A>G	p.Asn522Asp	missense	Exon 8 of 8	ENSP00000265074.8
	NPR3	ENST00000415167.2	TSL:1	c.1561A>G	p.Asn521Asp	missense	Exon 8 of 8	ENSP00000398028.2
	NPR3	ENST00000434067.6	TSL:5	c.916A>G	p.Asn306Asp	missense	Exon 8 of 8	ENSP00000388408.2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28373 AN: 152094 Hom.: 2891 Cov.: 32

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

GnomAD2 exomes AF: 0.207 AC: 49130 AN: 237278 AF XY: 0.210

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 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.: 25 AF XY: 0.214 AC XY: 152270 AN XY: 711392

African (AFR) AF: 0.106 AC: 3480 AN: 32944

American (AMR) AF: 0.206 AC: 8954 AN: 43546

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 3904 AN: 25834

East Asian (EAS) AF: 0.225 AC: 8854 AN: 39300

South Asian (SAS) AF: 0.269 AC: 22270 AN: 82878

European-Finnish (FIN) AF: 0.224 AC: 11912 AN: 53160

Middle Eastern (MID) AF: 0.110 AC: 629 AN: 5724

European-Non Finnish (NFE) AF: 0.214 AC: 231954 AN: 1086360

Other (OTH) AF: 0.198 AC: 11764 AN: 59278

GnomAD4 genome AF: 0.186 AC: 28380 AN: 152212 Hom.: 2889 Cov.: 32 AF XY: 0.191 AC XY: 14209 AN XY: 74406

African (AFR) AF: 0.112 AC: 4644 AN: 41548

American (AMR) AF: 0.225 AC: 3440 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 494 AN: 3472

East Asian (EAS) AF: 0.204 AC: 1055 AN: 5182

South Asian (SAS) AF: 0.282 AC: 1356 AN: 4816

European-Finnish (FIN) AF: 0.226 AC: 2399 AN: 10592

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14298 AN: 68002

Other (OTH) AF: 0.167 AC: 353 AN: 2114

Alfa AF: 0.203 Hom.: 14388

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

Submissions by phenotype

not provided Benign:3

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.067
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.055
Sift	Benign	0.31	T
Sift4G	Benign	0.22	T
Polyphen		0.0010	B
Vest4		0.039
ClinPred		0.015	T
GERP RS		5.0
Varity_R		0.14
gMVP		0.22
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2270915; hg19: chr5-32786389; COSMIC: COSV54084512; COSMIC: COSV54084512;