rs776553279
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_016373.4(WWOX):c.52C>A(p.Leu18Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. L18V) has been classified as Uncertain significance.
Frequency
Consequence
NM_016373.4 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WWOX | NM_016373.4 | c.52C>A | p.Leu18Met | missense_variant | 1/9 | ENST00000566780.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WWOX | ENST00000566780.6 | c.52C>A | p.Leu18Met | missense_variant | 1/9 | 1 | NM_016373.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1429580Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 708418
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Autosomal recessive spinocerebellar ataxia 12;C3463992:Developmental and epileptic encephalopathy, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2018 | This variant has not been reported in the literature in individuals with WWOX-related disease. 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with methionine at codon 18 of the WWOX protein (p.Leu18Met). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and methionine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at