rs1060499942

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001211.6(BUB1B):​c.1079C>G​(p.Pro360Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BUB1B
NM_001211.6 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09
Variant links:
Genes affected
BUB1B (HGNC:1149): (BUB1 mitotic checkpoint serine/threonine kinase B) This gene encodes a kinase involved in spindle checkpoint function. The protein has been localized to the kinetochore and plays a role in the inhibition of the anaphase-promoting complex/cyclosome (APC/C), delaying the onset of anaphase and ensuring proper chromosome segregation. Impaired spindle checkpoint function has been found in many forms of cancer. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BUB1BNM_001211.6 linkc.1079C>G p.Pro360Arg missense_variant Exon 9 of 23 ENST00000287598.11 NP_001202.5 O60566-1
LOC107984763XR_001751506.2 linkn.218-16364G>C intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BUB1BENST00000287598.11 linkc.1079C>G p.Pro360Arg missense_variant Exon 9 of 23 1 NM_001211.6 ENSP00000287598.7 O60566-1
BUB1BENST00000412359.7 linkc.1121C>G p.Pro374Arg missense_variant Exon 9 of 23 2 ENSP00000398470.3 O60566-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251046
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135776
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461556
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727078
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Mosaic variegated aneuploidy syndrome 1 Uncertain:1
Nov 10, 2016
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BUB1B-related disease. This sequence change replaces proline with arginine at codon 360 of the BUB1B protein (p.Pro360Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Uncertain
0.045
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.59
D;.
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.032
D
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-4.9
D;D
REVEL
Uncertain
0.47
Sift
Uncertain
0.0060
D;D
Sift4G
Benign
0.15
T;T
Polyphen
1.0
D;D
Vest4
0.57
MutPred
0.47
Gain of MoRF binding (P = 0.0013);.;
MVP
0.81
MPC
0.79
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.46
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1060499942; hg19: chr15-40488766; API