17-79094476-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001350451.2(RBFOX3):c.1052C>T(p.Ala351Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000302 in 1,325,652 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A351T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001350451.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBFOX3 | NM_001350451.2 | c.1052C>T | p.Ala351Val | missense_variant | 14/15 | ENST00000693108.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBFOX3 | ENST00000693108.1 | c.1052C>T | p.Ala351Val | missense_variant | 14/15 | NM_001350451.2 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD4 exome AF: 0.00000302 AC: 4AN: 1325652Hom.: 0 Cov.: 31 AF XY: 0.00000307 AC XY: 2AN XY: 651206
GnomAD4 genome ? Cov.: 30
ClinVar
Submissions by phenotype
Idiopathic generalized epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RBFOX3 protein function. This variant has not been reported in the literature in individuals affected with RBFOX3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 304 of the RBFOX3 protein (p.Ala304Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at