13-76995074-TC-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_006493.4(CLN5):c.187delC(p.Arg63ValfsTer51) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_006493.4 frameshift
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLN5 | NM_006493.4 | c.187delC | p.Arg63ValfsTer51 | frameshift_variant | Exon 2 of 4 | ENST00000377453.9 | NP_006484.2 | |
CLN5 | NM_001366624.2 | c.187delC | p.Arg63ValfsTer51 | frameshift_variant | Exon 2 of 5 | NP_001353553.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLN5 | ENST00000377453.9 | c.187delC | p.Arg63ValfsTer51 | frameshift_variant | Exon 2 of 4 | 1 | NM_006493.4 | ENSP00000366673.5 | ||
ENSG00000283208 | ENST00000638147.2 | c.187delC | p.Arg63ValfsTer51 | frameshift_variant | Exon 2 of 5 | 5 | ENSP00000490953.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Neuronal ceroid lipofuscinosis 5 Pathogenic:2
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Neuronal ceroid lipofuscinosis Pathogenic:1
ClinVar contains an entry for this variant (Variation ID: 527740). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with CLN5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg112Valfs*51) in the CLN5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLN5 are known to be pathogenic (PMID: 20157158). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at