15-75932822-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_147188.3(FBXO22):c.932C>T(p.Ala311Val) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,614,134 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
FBXO22
NM_147188.3 missense
NM_147188.3 missense
Scores
4
8
7
Clinical Significance
Conservation
PhyloP100: 7.09
Genes affected
FBXO22 (HGNC:13593): (F-box protein 22) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and, as a transcriptional target of the tumor protein p53, is thought to be involved in degradation of specific proteins in response to p53 induction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36168885).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBXO22 | NM_147188.3 | c.932C>T | p.Ala311Val | missense_variant | 7/7 | ENST00000308275.8 | NP_671717.1 | |
FBXO22 | XM_047432382.1 | c.620C>T | p.Ala207Val | missense_variant | 6/6 | XP_047288338.1 | ||
FBXO22 | NR_037623.2 | n.879C>T | non_coding_transcript_exon_variant | 6/6 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152240Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251306Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135834
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727248
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74380
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 11, 2022 | The c.932C>T (p.A311V) alteration is located in exon 7 (coding exon 7) of the FBXO22 gene. This alteration results from a C to T substitution at nucleotide position 932, causing the alanine (A) at amino acid position 311 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of relative solvent accessibility (P = 0.0071);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
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