rs748110754
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001350451.2(RBFOX3):c.166G>T(p.Glu56*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000845 in 1,183,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 8.5e-7 ( 0 hom. )
Consequence
RBFOX3
NM_001350451.2 stop_gained
NM_001350451.2 stop_gained
Scores
6
2
6
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.16
Publications
0 publications found
Genes affected
RBFOX3 (HGNC:27097): (RNA binding fox-1 homolog 3) This gene encodes a member of the RNA-binding FOX protein family which is involved in the regulation of alternative splicing of pre-mRNA. The protein has an N-terminal proline-rich region, an RNA recognition motif (RRM) domain, and a C-terminal alanine-rich region. This gene produces the neuronal nuclei (NeuN) antigen that has been widely used as a marker for post-mitotic neurons. This gene has its highest expression in the central nervous system and plays a prominent role in neural tissue development and regulation of adult brain function. Mutations in this gene have been associated with numerous neurological disorders. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2017]
RBFOX3 Gene-Disease associations (from GenCC):
- epilepsyInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| RBFOX3 | NM_001350451.2 | c.166G>T | p.Glu56* | stop_gained | Exon 5 of 15 | ENST00000693108.1 | NP_001337380.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RBFOX3 | ENST00000693108.1 | c.166G>T | p.Glu56* | stop_gained | Exon 5 of 15 | NM_001350451.2 | ENSP00000510395.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 8.45e-7 AC: 1AN: 1183230Hom.: 0 Cov.: 32 AF XY: 0.00000176 AC XY: 1AN XY: 568122 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1183230
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
568122
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
24020
American (AMR)
AF:
AC:
0
AN:
11944
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
16344
East Asian (EAS)
AF:
AC:
0
AN:
27416
South Asian (SAS)
AF:
AC:
0
AN:
41484
European-Finnish (FIN)
AF:
AC:
0
AN:
36658
Middle Eastern (MID)
AF:
AC:
0
AN:
4896
European-Non Finnish (NFE)
AF:
AC:
1
AN:
972204
Other (OTH)
AF:
AC:
0
AN:
48264
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;.;.;.;.
MetaRNN
Benign
.;.;.;.;.
MutationAssessor
Benign
.;.;.;.;.
PhyloP100
PROVEAN
Benign
.;.;.;.;.
REVEL
Benign
Sift
Pathogenic
.;.;.;.;.
Sift4G
Pathogenic
.;.;.;.;.
Vest4
GERP RS
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
Publications
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