rs145184714
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The ENST00000287598.11(BUB1B):c.1003G>A(p.Ala335Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,106 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A335P) has been classified as Likely benign.
Frequency
Consequence
ENST00000287598.11 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BUB1B | NM_001211.6 | c.1003G>A | p.Ala335Thr | missense_variant | 8/23 | ENST00000287598.11 | NP_001202.5 | |
LOC107984763 | XR_001751506.2 | n.218-5386C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BUB1B | ENST00000287598.11 | c.1003G>A | p.Ala335Thr | missense_variant | 8/23 | 1 | NM_001211.6 | ENSP00000287598 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251438Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135890
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727242
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74406
ClinVar
Submissions by phenotype
Mosaic variegated aneuploidy syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 27, 2023 | 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. 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 threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 938610). This variant has not been reported in the literature in individuals affected with BUB1B-related conditions. This variant is present in population databases (rs145184714, gnomAD 0.006%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 335 of the BUB1B protein (p.Ala335Thr). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 14, 2024 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at