chr22-35759931-C-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001349999.2(RBFOX2):c.1054G>T(p.Ala352Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000452 in 1,613,592 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 (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000046 ( 0 hom. )
Consequence
RBFOX2
NM_001349999.2 missense
NM_001349999.2 missense
Scores
8
8
Clinical Significance
Conservation
PhyloP100: 3.72
Genes affected
RBFOX2 (HGNC:9906): (RNA binding fox-1 homolog 2) This gene is one of several human genes similar to the C. elegans gene Fox-1. This gene encodes an RNA binding protein that is thought to be a key regulator of alternative exon splicing in the nervous system and other cell types. The protein binds to a conserved UGCAUG element found downstream of many alternatively spliced exons and promotes inclusion of the alternative exon in mature transcripts. The protein also interacts with the estrogen receptor 1 transcription factor and regulates estrogen receptor 1 transcriptional activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3179743).
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBFOX2 | NM_001349999.2 | c.1054G>T | p.Ala352Ser | missense_variant | 10/14 | ENST00000695854.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBFOX2 | ENST00000695854.1 | c.1054G>T | p.Ala352Ser | missense_variant | 10/14 | NM_001349999.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152118Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251260Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135794
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GnomAD4 exome AF: 0.0000458 AC: 67AN: 1461474Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27AN XY: 727052
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74326
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 07, 2022 | The c.1066G>T (p.A356S) alteration is located in exon 10 (coding exon 10) of the RBFOX2 gene. This alteration results from a G to T substitution at nucleotide position 1066, causing the alanine (A) at amino acid position 356 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;T;T;T;D;T;T
Polyphen
D;P;P;D;P;D;D;D
Vest4
MVP
MPC
2.1
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at