13-76996052-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_006493.4(CLN5):c.490G>T(p.Ala164Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_006493.4 missense
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.490G>T | p.Ala164Ser | missense_variant | Exon 3 of 4 | ENST00000377453.9 | NP_006484.2 | |
CLN5 | NM_001366624.2 | c.490G>T | p.Ala164Ser | missense_variant | Exon 3 of 5 | NP_001353553.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLN5 | ENST00000377453.9 | c.490G>T | p.Ala164Ser | missense_variant | Exon 3 of 4 | 1 | NM_006493.4 | ENSP00000366673.5 | ||
ENSG00000283208 | ENST00000638147.2 | c.490G>T | p.Ala164Ser | missense_variant | Exon 3 of 5 | 5 | ENSP00000490953.2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727248
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
Neuronal ceroid lipofuscinosis 5 Uncertain:2
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Neuronal ceroid lipofuscinosis Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 213 of the CLN5 protein (p.Ala213Ser). This variant is present in population databases (rs748549252, gnomAD 0.01%). 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: 566238). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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