16-28477524-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001042432.2(CLN3):c.1309C>T(p.Leu437Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,306 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_001042432.2 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 |
---|---|---|---|---|---|---|---|---|
CLN3 | NM_001042432.2 | c.1309C>T | p.Leu437Phe | missense_variant | Exon 16 of 16 | ENST00000636147.2 | NP_001035897.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLN3 | ENST00000636147.2 | c.1309C>T | p.Leu437Phe | missense_variant | Exon 16 of 16 | 1 | NM_001042432.2 | ENSP00000490105.1 | ||
ENSG00000261832 | ENST00000637378.1 | c.228+4581C>T | intron_variant | Intron 4 of 9 | 5 | ENSP00000490831.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461094Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726820
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74362
ClinVar
Submissions by phenotype
not provided Uncertain:1
A variant of uncertain significance has been identified in the CLN3 gene. The L437F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L437F variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L437F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at