rs751562146
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017882.3(CLN6):c.634C>T(p.Leu212Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,152 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. L212L) 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLN6 | NM_017882.3 | c.634C>T | p.Leu212Phe | missense_variant | 6/7 | ENST00000249806.11 | |
CLN6 | NM_001411068.1 | c.730C>T | p.Leu244Phe | missense_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLN6 | ENST00000249806.11 | c.634C>T | p.Leu212Phe | missense_variant | 6/7 | 1 | NM_017882.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251326Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135830
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461152Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726884
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Neuronal ceroid lipofuscinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 19, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 212 of the CLN6 protein (p.Leu212Phe). This variant is present in population databases (rs751562146, gnomAD 0.01%). 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: 575112). 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: "Tolerated"; 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