Variant chr15-40161242-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001211.6(BUB1B):c.22G>T(p.Gly8Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,834 control chromosomes in the GnomAD database, with no homozygous occurrence. 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

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BUB1B
NM_001211.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.277

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]

BUB1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.109722555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BUB1B	NM_001211.6 link	c.22G>T	p.Gly8Trp	missense_variant	Exon 1 of 23	ENST00000287598.11	NP_001202.5	O60566-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BUB1B	ENST00000287598.11 link	c.22G>T	p.Gly8Trp	missense_variant	Exon 1 of 23	1	NM_001211.6	ENSP00000287598.7		O60566-1
BUB1B	ENST00000412359.7 link	c.22G>T	p.Gly8Trp	missense_variant	Exon 1 of 23	2		ENSP00000398470.3		O60566-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460834

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726602

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 01, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with BUB1B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 8 of the BUB1B protein (p.Gly8Trp). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.081

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.069

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

0.88

P;.

Vest4

0.31

MutPred

0.24

Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);

MVP

0.30

MPC

0.43

ClinPred

0.42

GERP RS

0.76

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.1

Varity_R

0.095

gMVP

0.20

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over