13-76992003-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000636183(CLN5):c.-96C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000362 in 1,602,384 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
ENST00000636183 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLN5 | NM_006493.4 | c.-96C>T | upstream_gene_variant | ENST00000377453.9 | NP_006484.2 | |||
CLN5 | NM_001366624.2 | c.-96C>T | upstream_gene_variant | NP_001353553.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLN5 | ENST00000377453.9 | c.-96C>T | upstream_gene_variant | 1 | NM_006493.4 | ENSP00000366673.5 | ||||
ENSG00000283208 | ENST00000638147.2 | c.-96C>T | upstream_gene_variant | 5 | ENSP00000490953.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000791 AC: 17AN: 214828Hom.: 1 AF XY: 0.000109 AC XY: 13AN XY: 119528
GnomAD4 exome AF: 0.0000379 AC: 55AN: 1450204Hom.: 1 Cov.: 34 AF XY: 0.0000499 AC XY: 36AN XY: 721034
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74348
ClinVar
Submissions by phenotype
Neuronal ceroid lipofuscinosis 5 Uncertain:2
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not provided Uncertain:1
Has not been previously published as pathogenic or benign to our knowledge -
Neuronal ceroid lipofuscinosis Uncertain:1
This sequence change creates a premature translational stop signal (p.Gln18*) in the CLN5 gene. However, it is currently unclear if variants that occur in this region of the gene cause disease. This variant is present in population databases (rs773979248, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with CLN5-related conditions. ClinVar contains an entry for this variant (Variation ID: 421520). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at