Variant 5-55128425-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001170402.1(CDC20B):c.890T>A(p.Val297Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000318 in 1,447,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

CDC20B
NM_001170402.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

Variant links:

Genes affected

CDC20B (HGNC:24222): (cell division cycle 20B) Predicted to enable anaphase-promoting complex binding activity and ubiquitin ligase activator activity. Predicted to be involved in anaphase-promoting complex-dependent catabolic process and positive regulation of anaphase-promoting complex-dependent catabolic process. Predicted to be part of anaphase-promoting complex. [provided by Alliance of Genome Resources, Apr 2022]

CDC20B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.94

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC20B	NM_001170402.1 linkuse as main transcript	c.890T>A	p.Val297Glu	missense_variant	7/12	ENST00000381375.7	NP_001163873.1	Q86Y33-1
CDC20B	NM_152623.2 linkuse as main transcript	c.890T>A	p.Val297Glu	missense_variant	7/12		NP_689836.2	Q86Y33-2
CDC20B	NM_001145734.2 linkuse as main transcript	c.890T>A	p.Val297Glu	missense_variant	7/11		NP_001139206.2	Q86Y33-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDC20B	ENST00000381375.7 linkuse as main transcript	c.890T>A	p.Val297Glu	missense_variant	7/12	1	NM_001170402.1	ENSP00000370781.2	Q86Y33-1
CDC20B	ENST00000296733.5 linkuse as main transcript	c.890T>A	p.Val297Glu	missense_variant	7/12	1		ENSP00000296733.1	Q86Y33-2
CDC20B	ENST00000322374.10 linkuse as main transcript	c.890T>A	p.Val297Glu	missense_variant	7/11	1		ENSP00000315720.6	Q86Y33-3
CDC20B	ENST00000513180.5 linkuse as main transcript	n.890T>A		non_coding_transcript_exon_variant	7/12	5		ENSP00000426776.1	Q86Y33-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000424

AC:

AN:

236080

Hom.:

AF XY:

0.00000784

AC XY:

AN XY:

127584

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:

0.00000916

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000318

AC:

AN:

1447184

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

719552

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:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000397

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Mar 14, 2023

The c.890T>A (p.V297E) alteration is located in exon 7 (coding exon 7) of the CDC20B gene. This alteration results from a T to A substitution at nucleotide position 890, causing the valine (V) at amino acid position 297 to be replaced by a glutamic acid (E). 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

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

.;T;.

Eigen

Pathogenic

0.76

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Uncertain

-0.14

MutationAssessor

Pathogenic

3.6

H;H;H

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.3

D;D;D

REVEL

Uncertain

0.48

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.85

MutPred

0.80

Gain of disorder (P = 0.0017);Gain of disorder (P = 0.0017);Gain of disorder (P = 0.0017);

MVP

0.57

MPC

1.0

ClinPred

0.99

GERP RS

4.6

Varity_R

0.90

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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