NM_001211.6:c.1397A>C
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001211.6(BUB1B):c.1397A>C(p.Asp466Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,610,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D466H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001211.6 missense
Scores
Clinical Significance
Conservation
Publications
- mosaic variegated aneuploidy syndrome 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P
- rhabdomyosarcomaInheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
- mosaic variegated aneuploidy syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BUB1B | ENST00000287598.11 | c.1397A>C | p.Asp466Ala | missense_variant | Exon 10 of 23 | 1 | NM_001211.6 | ENSP00000287598.7 | ||
BUB1B | ENST00000412359.7 | c.1439A>C | p.Asp480Ala | missense_variant | Exon 10 of 23 | 2 | ENSP00000398470.3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152262Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000120 AC: 3AN: 250970 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.0000343 AC: 50AN: 1458342Hom.: 0 Cov.: 29 AF XY: 0.0000248 AC XY: 18AN XY: 725688 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74390 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Mosaic variegated aneuploidy syndrome 1 Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 466 of the BUB1B protein (p.Asp466Ala). This variant is present in population databases (rs587778140, gnomAD 0.002%). 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: 133765). 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. -
not specified Other:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at