5-32711863-T-TGGC
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2
The NM_001204375.2(NPR3):c.99_101dup(p.Gly34dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,463,164 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000076 ( 0 hom. )
Consequence
NPR3
NM_001204375.2 inframe_insertion
NM_001204375.2 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.813
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP3
?
Nonframeshift variant in repetitive region in NM_001204375.2
BS2
?
High AC in GnomAdExome at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPR3 | NM_001204375.2 | c.99_101dup | p.Gly34dup | inframe_insertion | 1/8 | ENST00000265074.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPR3 | ENST00000265074.13 | c.99_101dup | p.Gly34dup | inframe_insertion | 1/8 | 1 | NM_001204375.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151824Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000866 AC: 6AN: 69280Hom.: 0 AF XY: 0.0000858 AC XY: 3AN XY: 34964
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GnomAD4 exome AF: 0.00000763 AC: 10AN: 1311340Hom.: 0 Cov.: 35 AF XY: 0.00000938 AC XY: 6AN XY: 639854
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with NPR3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.08%). This variant, c.99_101dup, results in the insertion of 1 amino acid(s) of the NPR3 protein (p.Gly35dup), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at