15-40161246-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001211.6(BUB1B):c.26G>C(p.Gly9Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★★).
Frequency
Consequence
NM_001211.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246332Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133482
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.G9A variant (also known as c.26G>C), located in coding exon 1 of the BUB1B gene, results from a G to C substitution at nucleotide position 26. The glycine at codon 9 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Mosaic variegated aneuploidy syndrome 1 Uncertain:1
This sequence change replaces glycine with alanine at codon 9 of the BUB1B protein (p.Gly9Ala). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and alanine. This variant is present in population databases (rs768279736, ExAC 0.01%). This variant has not been reported in the literature in individuals with BUB1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 575983). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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