Variant 5-32711819-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001204375.2(NPR3):c.43C>G(p.Leu15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000767 in 1,304,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

NPR3
NM_001204375.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.832

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20579499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPR3	NM_001204375.2 linkuse as main transcript	c.43C>G	p.Leu15Val	missense_variant	1/8	ENST00000265074.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPR3	ENST00000265074.13 linkuse as main transcript	c.43C>G	p.Leu15Val	missense_variant	1/8	1	NM_001204375.2	P4	P17342-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.67e-7

AC:

AN:

1304226

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

634916

show subpopulations

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:

0.0000159

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.43C>G (p.L15V) alteration is located in exon 1 (coding exon 1) of the NPR3 gene. This alteration results from a C to G substitution at nucleotide position 43, causing the leucine (L) at amino acid position 15 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.085

T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.71

T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.32

N;N

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.24

T;T

Polyphen

0.016

B;.

Vest4

0.26

MutPred

0.43

Gain of sheet (P = 0.0073);Gain of sheet (P = 0.0073);

MVP

0.82

ClinPred

0.52

GERP RS

2.7

Varity_R

0.21

gMVP

0.59

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over