rs776842972
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004937.3(CTNS):c.870C>G(p.Tyr290Ter) variant causes a stop gained change involving the alteration of a non-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 Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Y290Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_004937.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTNS | NM_004937.3 | c.870C>G | p.Tyr290Ter | stop_gained | 11/12 | ENST00000046640.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTNS | ENST00000046640.9 | c.870C>G | p.Tyr290Ter | stop_gained | 11/12 | 1 | NM_004937.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Cystinosis Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 20, 2021 | Variant summary: CTNS c.870C>G (p.Tyr290X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250904 control chromosomes (gnomAD). c.870C>G has been reported in at least one homozygous individual affected with Cystinosis (example: Shotelersuk_1998). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 15, 2016 | The p.Tyr290X variant in CTNS has been reported in 1 patient with nephropathic c ystinosis in the homozygous state (Shotelersuk 1998) and was absent from large p opulation studies. This nonsense variant leads to a premature termination codon at position 290, which is predicted to lead to a truncated or absent protein. Bi allelic loss of function of the CTNS gene is associated with nephropathic cystin osis. In summary, the p.Tyr290X variant meets our criteria to be classified as p athogenic for nephropathic cystinosis in an autosomal recessive manner based upo n its predicted functional impact, homozygous identification in an affected indi vidual, and absence from controls. - |
Nephropathic cystinosis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 20, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at