rs1555812114
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018723.4(RBFOX1):c.1040C>T(p.Ala347Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
RBFOX1
NM_018723.4 missense
NM_018723.4 missense
Scores
2
9
6
Clinical Significance
Conservation
PhyloP100: 5.44
Genes affected
RBFOX1 (HGNC:18222): (RNA binding fox-1 homolog 1) The Fox-1 family of RNA-binding proteins is evolutionarily conserved, and regulates tissue-specific alternative splicing in metazoa. Fox-1 recognizes a (U)GCAUG stretch in regulated exons or in flanking introns. The protein binds to the C-terminus of ataxin-2 and may contribute to the restricted pathology of spinocerebellar ataxia type 2 (SCA2). Ataxin-2 is the product of the SCA2 gene which causes familial neurodegenerative diseases. Fox-1 and ataxin-2 are both localized in the trans-Golgi network. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBFOX1 | NM_018723.4 | c.1040C>T | p.Ala347Val | missense_variant | 15/16 | ENST00000550418.6 | |
RBFOX1 | NM_145893.3 | c.1156C>T | p.Leu386Phe | missense_variant | 13/14 | ENST00000355637.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBFOX1 | ENST00000550418.6 | c.1040C>T | p.Ala347Val | missense_variant | 15/16 | 1 | NM_018723.4 | A1 | |
RBFOX1 | ENST00000355637.9 | c.1156C>T | p.Leu386Phe | missense_variant | 13/14 | 1 | NM_145893.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461228Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726890
GnomAD4 exome
AF:
AC:
2
AN:
1461228
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
726890
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Idiopathic generalized epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 23, 2019 | 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RBFOX1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 368 of the RBFOX1 protein (p.Ala368Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N;N;N;N;N;.
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;.
Sift4G
Uncertain
D;D;D;D;D;D;D;D
Polyphen
B;B;P;B;P;P;.;.
Vest4
MutPred
0.34
.;.;Loss of disorder (P = 0.0538);.;.;.;.;.;
MVP
MPC
1.5
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at