12-117158024-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015002.3(FBXO21):c.1366G>A(p.Gly456Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000743 in 1,614,092 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
FBXO21
NM_015002.3 missense
NM_015002.3 missense
Scores
1
5
8
Clinical Significance
Conservation
PhyloP100: 6.35
Genes affected
FBXO21 (HGNC:13592): (F-box protein 21) 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 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. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21565631).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBXO21 | NM_015002.3 | c.1366G>A | p.Gly456Arg | missense_variant | 10/12 | ENST00000622495.5 | |
FBXO21 | NM_033624.3 | c.1387G>A | p.Gly463Arg | missense_variant | 10/12 | ||
FBXO21 | XM_017019037.3 | c.1207G>A | p.Gly403Arg | missense_variant | 9/11 | ||
FBXO21 | XM_017019038.3 | c.1186G>A | p.Gly396Arg | missense_variant | 9/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBXO21 | ENST00000622495.5 | c.1366G>A | p.Gly456Arg | missense_variant | 10/12 | 1 | NM_015002.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251434Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135880
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727244
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74356
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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 | Jan 10, 2022 | The c.1387G>A (p.G463R) alteration is located in exon 10 (coding exon 10) of the FBXO21 gene. This alteration results from a G to A substitution at nucleotide position 1387, causing the glycine (G) at amino acid position 463 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D;D
Polyphen
B;.;P;.
Vest4
MutPred
0.40
.;.;Gain of solvent accessibility (P = 0.0471);.;
MVP
MPC
1.2
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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