chr11-77115423-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3PP5_Moderate
The NM_004055.5(CAPN5):c.728G>T(p.Arg243Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R243H) has been classified as Uncertain significance.
Frequency
Consequence
NM_004055.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN5 | NM_004055.5 | c.728G>T | p.Arg243Leu | missense_variant | 6/13 | ENST00000648180.1 | |
CAPN5 | XM_011545225.1 | c.848G>T | p.Arg283Leu | missense_variant | 7/14 | ||
CAPN5 | XM_017018223.3 | c.836G>T | p.Arg279Leu | missense_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN5 | ENST00000648180.1 | c.728G>T | p.Arg243Leu | missense_variant | 6/13 | NM_004055.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Proliferative vitreoretinopathy Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2012 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 243 of the CAPN5 protein (p.Arg243Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant neovascular inflammatory vitreoretinopathy (PMID: 23055945). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 39806). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CAPN5 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects CAPN5 function (PMID: 23055945, 24381307, 25994508). For these reasons, this variant has been classified as Pathogenic. - |
Autosomal dominant neovascular inflammatory vitreoretinopathy Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Pathogenic and reported on 11-05-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at