15-68214373-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017882.3(CLN6):c.214G>A(p.Glu72Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,613,622 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E72Q) has been classified as Likely benign.
Frequency
Consequence
NM_017882.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLN6 | NM_017882.3 | c.214G>A | p.Glu72Lys | missense_variant | Exon 3 of 7 | ENST00000249806.11 | NP_060352.1 | |
CLN6 | NM_001411068.1 | c.310G>A | p.Glu104Lys | missense_variant | Exon 3 of 7 | NP_001397997.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251428Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135902
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461402Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25AN XY: 727038
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
not provided Uncertain:1
Not observed at significant frequency in large population cohorts (Lek et al., 2016); 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 -
Neuronal ceroid lipofuscinosis Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 72 of the CLN6 protein (p.Glu72Lys). This variant is present in population databases (rs104894483, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CLN6-related conditions. ClinVar contains an entry for this variant (Variation ID: 964655). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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