5-32742359-C-T

Variant names:

• chr5-32742359-C-T
• rs765199
• NM_001204375.2:c.1059+3329C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204375.2(NPR3):​c.1059+3329C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,870 control chromosomes in the GnomAD database, including 4,140 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4140 hom., cov: 31)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1059+3329C>T		intron_variant	Intron 3 of 7	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.1059+3329C>T		intron_variant	Intron 3 of 7	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35182 AN: 151752 Hom.: 4137 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.232 AC: 35227 AN: 151870 Hom.: 4140 Cov.: 31 AF XY: 0.233 AC XY: 17263 AN XY: 74226

African (AFR) AF: 0.230 AC: 9503 AN: 41362

American (AMR) AF: 0.265 AC: 4037 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3464

East Asian (EAS) AF: 0.245 AC: 1266 AN: 5162

South Asian (SAS) AF: 0.310 AC: 1491 AN: 4812

European-Finnish (FIN) AF: 0.175 AC: 1852 AN: 10556

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15398 AN: 67952

Other (OTH) AF: 0.218 AC: 459 AN: 2106

Alfa AF: 0.125 Hom.: 219

Bravo AF: 0.236

Asia WGS AF: 0.288 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.28
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs765199; hg19: chr5-32742465;