rs137858807
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000636147.2(CLN3):c.776C>T(p.Pro259Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000064 in 1,609,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P259Q) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000636147.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLN3 | NM_001042432.2 | c.776C>T | p.Pro259Leu | missense_variant | 10/16 | ENST00000636147.2 | NP_001035897.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLN3 | ENST00000636147.2 | c.776C>T | p.Pro259Leu | missense_variant | 10/16 | 1 | NM_001042432.2 | ENSP00000490105 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000289 AC: 44AN: 152100Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000539 AC: 13AN: 241400Hom.: 0 AF XY: 0.0000383 AC XY: 5AN XY: 130540
GnomAD4 exome AF: 0.0000405 AC: 59AN: 1456974Hom.: 0 Cov.: 30 AF XY: 0.0000373 AC XY: 27AN XY: 724270
GnomAD4 genome AF: 0.000289 AC: 44AN: 152218Hom.: 0 Cov.: 31 AF XY: 0.000228 AC XY: 17AN XY: 74438
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 27, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 21, 2020 | 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 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 26, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2022 | The p.P259L variant (also known as c.776C>T), located in coding exon 9 of the CLN3 gene, results from a C to T substitution at nucleotide position 776. The proline at codon 259 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Neuronal ceroid lipofuscinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 15, 2024 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 259 of the CLN3 protein (p.Pro259Leu). This variant is present in population databases (rs137858807, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with CLN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 193616). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Neuronal ceroid lipofuscinosis 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at