10-5903166-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_178150.3(FBH1):c.148G>A(p.Gly50Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000763 in 1,609,310 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00040 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00080 ( 2 hom. )
Consequence
FBH1
NM_178150.3 missense
NM_178150.3 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.478
Genes affected
FBH1 (HGNC:13620): (F-box DNA helicase 1) This gene encodes a member of the F-box protein family, members of which are 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 three 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 Fbx class. It contains an F-box motif and seven conserved helicase motifs, and has both DNA-dependent ATPase and DNA unwinding activities. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.015186697).
BS2
High AC in GnomAd4 at 61 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBH1 | NM_178150.3 | c.148G>A | p.Gly50Arg | missense_variant | 2/21 | ENST00000362091.9 | NP_835363.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBH1 | ENST00000362091.9 | c.148G>A | p.Gly50Arg | missense_variant | 2/21 | 1 | NM_178150.3 | ENSP00000355415.4 |
Frequencies
GnomAD3 genomes AF: 0.000401 AC: 61AN: 152150Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000355 AC: 88AN: 248206Hom.: 0 AF XY: 0.000283 AC XY: 38AN XY: 134224
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GnomAD4 exome AF: 0.000801 AC: 1167AN: 1457160Hom.: 2 Cov.: 30 AF XY: 0.000776 AC XY: 562AN XY: 724578
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GnomAD4 genome AF: 0.000401 AC: 61AN: 152150Hom.: 0 Cov.: 31 AF XY: 0.000309 AC XY: 23AN XY: 74346
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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 | Sep 04, 2024 | The c.301G>A (p.G101R) alteration is located in exon 3 (coding exon 3) of the FBXO18 gene. This alteration results from a G to A substitution at nucleotide position 301, causing the glycine (G) at amino acid position 101 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
.;T
Polyphen
B;B
Vest4
MutPred
Gain of MoRF binding (P = 0.052);.;
MVP
MPC
0.14
ClinPred
T
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