2-47839485-T-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_001190274.2(FBXO11):āc.376A>Gā(p.Thr126Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T126S) has been classified as Likely benign.
Frequency
Consequence
NM_001190274.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250696Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135606
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461640Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727072
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74496
ClinVar
Submissions by phenotype
Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jul 30, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 20, 2023 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 126 of the FBXO11 protein (p.Thr126Ala). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with FBXO11-related conditions. ClinVar contains an entry for this variant (Variation ID: 1375464). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at