chr15-68229523-C-CCCG
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_017882.3(CLN6):c.61_62insCGG(p.Leu20_Gly21insAla) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000818 in 1,467,142 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G21G) has been classified as Likely benign.
Frequency
Consequence
NM_017882.3 inframe_insertion
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLN6 | NM_017882.3 | c.61_62insCGG | p.Leu20_Gly21insAla | inframe_insertion | 1/7 | ENST00000249806.11 | |
CLN6 | NM_001411068.1 | c.180-10874_180-10873insCGG | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLN6 | ENST00000249806.11 | c.61_62insCGG | p.Leu20_Gly21insAla | inframe_insertion | 1/7 | 1 | NM_017882.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151992Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000836 AC: 11AN: 1315150Hom.: 0 Cov.: 31 AF XY: 0.0000108 AC XY: 7AN XY: 648416
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151992Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74256
ClinVar
Submissions by phenotype
Neuronal ceroid lipofuscinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2019 | This sequence change inserts 3 nucleotides in exon 1 of the CLN6 mRNA (c.61_62insCGG). This leads to the insertion of 1 amino acid residue in the CLN6 protein (p.Leu20_Gly21insAla) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CLN6-related disease. While this variant is not present in population databases (ExAC), the frequency information is unreliable due to low sequence coverage at this site. In summary, this is a novel in-frame insertion with uncertain impact on protein function. 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