16-78114996-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_016373.4(WWOX):c.251C>G(p.Thr84Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,614,080 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T84T) has been classified as Likely benign.
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.251C>G | p.Thr84Ser | missense_variant | 4/9 | ENST00000566780.6 | |
WWOX | NM_130791.5 | c.251C>G | p.Thr84Ser | missense_variant | 4/6 | ||
WWOX | NM_001291997.2 | c.-89C>G | 5_prime_UTR_variant | 3/8 | |||
WWOX | NR_120436.3 | n.490C>G | non_coding_transcript_exon_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WWOX | ENST00000566780.6 | c.251C>G | p.Thr84Ser | missense_variant | 4/9 | 1 | NM_016373.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249562Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135398
GnomAD4 exome AF: 0.0000677 AC: 99AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.0000715 AC XY: 52AN XY: 727242
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344
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 | Mar 24, 2023 | ClinVar contains an entry for this variant (Variation ID: 426908). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with WWOX-related conditions. This variant is present in population databases (rs757145186, gnomAD 0.007%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 84 of the WWOX protein (p.Thr84Ser). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 20, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); 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 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at