rs200771165
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 1P and 18B. PP2BP4_ModerateBP6_Very_StrongBS1BS2
The NM_001190274.2(FBXO11):āc.2491A>Gā(p.Ser831Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000307 in 1,606,812 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.00024 ( 0 hom., cov: 33)
Exomes š: 0.00031 ( 0 hom. )
Consequence
FBXO11
NM_001190274.2 missense
NM_001190274.2 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: 5.99
Genes affected
FBXO11 (HGNC:13590): (F-box protein 11) 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. It can function as an arginine methyltransferase that symmetrically dimethylates arginine residues, and it acts as an adaptor protein to mediate the neddylation of p53, which leads to the suppression of p53 function. This gene is known to be down-regulated in melanocytes from patients with vitiligo, a skin disorder that results in depigmentation. Polymorphisms in this gene are associated with chronic otitis media with effusion and recurrent otitis media (COME/ROM), a hearing loss disorder, and the knockout of the homologous mouse gene results in the deaf mouse mutant Jeff (Jf), a single gene model of otitis media. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2010]
MSH6 (HGNC:7329): (mutS homolog 6) This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, FBXO11
BP4
?
Computational evidence support a benign effect (MetaRNN=0.24323764).
BP6
?
Variant 2-47809222-T-C is Benign according to our data. Variant chr2-47809222-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 134376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47809222-T-C is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000243 (37/152352) while in subpopulation NFE AF= 0.000367 (25/68036). AF 95% confidence interval is 0.000255. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 37 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBXO11 | NM_001190274.2 | c.2491A>G | p.Ser831Gly | missense_variant | 21/23 | ENST00000403359.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBXO11 | ENST00000403359.8 | c.2491A>G | p.Ser831Gly | missense_variant | 21/23 | 1 | NM_001190274.2 |
Frequencies
GnomAD3 genomes ? AF: 0.000243 AC: 37AN: 152234Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000225 AC: 56AN: 248392Hom.: 0 AF XY: 0.000216 AC XY: 29AN XY: 134166
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GnomAD4 exome AF: 0.000314 AC: 457AN: 1454460Hom.: 0 Cov.: 27 AF XY: 0.000316 AC XY: 229AN XY: 723812
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GnomAD4 genome ? AF: 0.000243 AC: 37AN: 152352Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74504
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Neurodevelopmental disorder Uncertain:1
Uncertain significance, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 30, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Vest4
MVP
MPC
1.3
ClinPred
T
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