15-40161243-G-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001211.6(BUB1B):c.23G>C(p.Gly8Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000203 AC: 5AN: 246734Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133730
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460852Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726602
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74468
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.G8A variant (also known as c.23G>C), located in coding exon 1 of the BUB1B gene, results from a G to C substitution at nucleotide position 23. The glycine at codon 8 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, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 8 of the BUB1B protein (p.Gly8Ala). This variant is present in population databases (rs554782320, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BUB1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1019330). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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