Variant chrX-50308731-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_033031.3(CCNB3):c.562T>A(p.Ser188Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000736 in 1,209,091 control chromosomes in the GnomAD database, including 6 homozygotes. There are 242 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., 107 hem., cov: 22)

Exomes 𝑓: 0.00044 ( 3 hom. 135 hem. )

Consequence

CCNB3
NM_033031.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.412

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006671548).

BP6

Variant X-50308731-T-A is Benign according to our data. Variant chrX-50308731-T-A is described in ClinVar as [Benign]. Clinvar id is 727698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNB3	NM_033031.3 linkuse as main transcript	c.562T>A	p.Ser188Thr	missense_variant	6/13	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.562T>A	p.Ser188Thr	missense_variant	6/13	2	NM_033031.3	ENSP00000365210.1		Q8WWL7-1

Frequencies

GnomAD3 genomes

AF:

0.00371

AC:

414

AN:

111522

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

107

AN XY:

33732

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00114

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00265

GnomAD3 exomes

AF:

0.00109

AC:

199

AN:

182708

Hom.:

AF XY:

0.000756

AC XY:

AN XY:

67444

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000525

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.000666

GnomAD4 exome

AF:

0.000436

AC:

478

AN:

1097514

Hom.:

Cov.:

AF XY:

0.000372

AC XY:

135

AN XY:

362904

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.00122

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000739

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.00122

GnomAD4 genome

AF:

0.00369

AC:

412

AN:

111577

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

107

AN XY:

33797

show subpopulations

Gnomad4 AFR

AF:

0.0128

Gnomad4 AMR

AF:

0.00114

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:

0.00262

Alfa

AF:

0.000441

Hom.:

Bravo

AF:

0.00372

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.0123

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00121

AC:

147

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.46

DANN

Benign

0.91

DEOGEN2

Benign

0.083

T;T

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.37

.;T

MetaRNN

Benign

0.0067

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.033

Sift

Benign

0.97

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.90

P;P

Vest4

0.19

MVP

0.54

MPC

0.37

ClinPred

0.012

GERP RS

-2.2

Varity_R

0.073

gMVP

0.13

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