chr5-32786283-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001204375.2(NPR3):​c.1564A>T​(p.Asn522Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1564A>T	p.Asn522Tyr	missense_variant	Exon 8 of 8	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.1564A>T	p.Asn522Tyr	missense_variant	Exon 8 of 8	1	NM_001204375.2	ENSP00000265074.8
NPR3	ENST00000415167.2	c.1561A>T	p.Asn521Tyr	missense_variant	Exon 8 of 8	1		ENSP00000398028.2
NPR3	ENST00000434067.6	c.916A>T	p.Asn306Tyr	missense_variant	Exon 8 of 8	5		ENSP00000388408.2
NPR3	ENST00000326958.5	c.913A>T	p.Asn305Tyr	missense_variant	Exon 8 of 8	2		ENSP00000318340.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1435950 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 714600

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;.;T;.
Eigen	Benign	-0.052
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.66	D;D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	.;.;L;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.4	N;.;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0040	D;.;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.88	.;.;P;.
Vest4		0.62
MutPred		0.13		.;.;Loss of loop (P = 0.0374);.;
MVP		0.80
ClinPred		0.95	D
GERP RS		5.0
Varity_R		0.16
gMVP		0.40

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

Other links and lift over

dbSNP: rs2270915; hg19: chr5-32786389;