rs2270915

Positions:

• chr5-32786283-A-C
• chr5-32786283-A-G
• chr5-32786283-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001204375.2(NPR3):​c.1564A>C​(p.Asn522His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPR3 NM_001204375.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3065331).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1564A>C	p.Asn522His	missense_variant	8/8	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.1564A>C	p.Asn522His	missense_variant	8/8	1	NM_001204375.2	ENSP00000265074	P4
NPR3	ENST00000415167.2	c.1561A>C	p.Asn521His	missense_variant	8/8	1		ENSP00000398028	A1
NPR3	ENST00000434067.6	c.916A>C	p.Asn306His	missense_variant	8/8	5		ENSP00000388408
NPR3	ENST00000326958.5	c.913A>C	p.Asn305His	missense_variant	8/8	2		ENSP00000318340

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;.;T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.091
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	.;.;L;.
MutationTaster	Benign	0.019	P;P;P;P
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.97	N;.;N;N
REVEL	Benign	0.042
Sift	Benign	0.20	T;.;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.030	.;.;B;.
Vest4		0.20
MutPred		0.097		.;.;Loss of solvent accessibility (P = 0.0249);.;
MVP		0.79
ClinPred		0.89	D
GERP RS		5.0
Varity_R		0.14
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2270915; hg19: chr5-32786389;