Variant chrX-50288823-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_033031.3(CCNB3):c.140A>G(p.Gln47Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,207,321 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., 5 hem., cov: 22)

Exomes 𝑓: 0.000016 ( 0 hom. 5 hem. )

Consequence

CCNB3
NM_033031.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.234

Variant links:

Genes affected

CCNB3 (HGNC:18709): (cyclin B3) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as positive regulators of cyclin-dependent kinases (CDKs), and thereby play an essential role in the control of the cell cycle. Different cyclins exhibit distinct expression and degradation patterns, which contribute to the temporal coordination of each mitotic event. Studies of similar genes in chicken and drosophila suggest that this cyclin may associate with CDC2 and CDK2 kinases, and may be required for proper spindle reorganization and restoration of the interphase nucleus. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

CCNB3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04626903).

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNB3	NM_033031.3 linkuse as main transcript	c.140A>G	p.Gln47Arg	missense_variant	4/13	ENST00000376042.6	NP_149020.2	Q8WWL7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNB3	ENST00000376042.6 linkuse as main transcript	c.140A>G	p.Gln47Arg	missense_variant	4/13	2	NM_033031.3	ENSP00000365210.1		Q8WWL7-1

Frequencies

GnomAD3 genomes

AF:

0.0000896

AC:

AN:

111627

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

33839

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000859

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000333

AC:

AN:

180368

Hom.:

AF XY:

0.0000307

AC XY:

AN XY:

65086

show subpopulations

Gnomad AFR exome

AF:

0.0000770

Gnomad AMR exome

AF:

0.0000367

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:

0.0000249

Gnomad OTH exome

AF:

0.000448

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1095694

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

361218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.000227

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:

0.00000714

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.0000896

AC:

AN:

111627

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

33839

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000859

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000174

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2023

The c.140A>G (p.Q47R) alteration is located in exon 3 (coding exon 2) of the CCNB3 gene. This alteration results from a A to G substitution at nucleotide position 140, causing the glutamine (Q) at amino acid position 47 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.9

DANN

Benign

0.95

DEOGEN2

Benign

0.020

T;.;T;.

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.37

.;.;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.046

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.41

N;N;N;N

REVEL

Benign

0.028

Sift

Benign

0.066

T;D;T;D

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.054

B;B;B;B

Vest4

0.15

MutPred

0.094

Gain of MoRF binding (P = 0.0504);Gain of MoRF binding (P = 0.0504);Gain of MoRF binding (P = 0.0504);Gain of MoRF binding (P = 0.0504);

MVP

0.23

MPC

0.19

ClinPred

0.013

GERP RS

0.15

Varity_R

0.25

gMVP

0.097

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over