rs777276873
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_153240.5(NPHP3):āc.3287T>Cā(p.Leu1096Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1096F) has been classified as Uncertain significance.
Frequency
Consequence
NM_153240.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHP3 | NM_153240.5 | c.3287T>C | p.Leu1096Pro | missense_variant | 23/27 | ENST00000337331.10 | |
NPHP3-ACAD11 | NR_037804.1 | n.3293T>C | non_coding_transcript_exon_variant | 22/45 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHP3 | ENST00000337331.10 | c.3287T>C | p.Leu1096Pro | missense_variant | 23/27 | 1 | NM_153240.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251474Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135906
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461612Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727114
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74362
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Likely pathogenic, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 16, 2021 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31589614) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at