16-7518318-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_018723.4(RBFOX1):c.199C>T(p.Pro67Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000291 in 1,613,980 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. P67A) has been classified as Uncertain significance.
Frequency
Consequence
NM_018723.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBFOX1 | NM_018723.4 | c.199C>T | p.Pro67Ser | missense_variant | 5/16 | ENST00000550418.6 | |
RBFOX1 | NM_145893.3 | c.259C>T | p.Pro87Ser | missense_variant | 2/14 | ENST00000355637.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBFOX1 | ENST00000550418.6 | c.199C>T | p.Pro67Ser | missense_variant | 5/16 | 1 | NM_018723.4 | A1 | |
RBFOX1 | ENST00000355637.9 | c.259C>T | p.Pro87Ser | missense_variant | 2/14 | 1 | NM_145893.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251218Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135760
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461810Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25AN XY: 727210
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74328
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 11, 2022 | The c.259C>T (p.P87S) alteration is located in exon 2 (coding exon 2) of the RBFOX1 gene. This alteration results from a C to T substitution at nucleotide position 259, causing the proline (P) at amino acid position 87 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Idiopathic generalized epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 87 of the RBFOX1 protein (p.Pro87Ser). This variant is present in population databases (rs143573994, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with RBFOX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 241956). 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 RBFOX1 protein function with a negative predictive value of 80%. 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