Variant 5-55124837-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001170402.1(CDC20B):c.1181C>T(p.Pro394Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000688 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

CDC20B
NM_001170402.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4017853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDC20B	NM_001170402.1 linkuse as main transcript	c.1181C>T	p.Pro394Leu	missense_variant	9/12	ENST00000381375.7
CDC20B	NM_152623.2 linkuse as main transcript	c.1181C>T	p.Pro394Leu	missense_variant	9/12
CDC20B	NM_001145734.2 linkuse as main transcript	c.1181C>T	p.Pro394Leu	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC20B	ENST00000381375.7 linkuse as main transcript	c.1181C>T	p.Pro394Leu	missense_variant	9/12	1	NM_001170402.1	A1	Q86Y33-1
CDC20B	ENST00000296733.5 linkuse as main transcript	c.1181C>T	p.Pro394Leu	missense_variant	9/12	1		P4	Q86Y33-2
CDC20B	ENST00000322374.10 linkuse as main transcript	c.1181C>T	p.Pro394Leu	missense_variant	9/11	1			Q86Y33-3
CDC20B	ENST00000513180.5 linkuse as main transcript	c.*148C>T		3_prime_UTR_variant, NMD_transcript_variant	10/12	5			Q86Y33-4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

251112

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000711

AC:

104

AN:

1461808

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000854

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Oct 05, 2022

The c.1181C>T (p.P394L) alteration is located in exon 9 (coding exon 9) of the CDC20B gene. This alteration results from a C to T substitution at nucleotide position 1181, causing the proline (P) at amino acid position 394 to be replaced by a leucine (L). 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

0.18

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.37

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

0.15

Eigen_PC

Benign

0.035

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Pathogenic

3.1

M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-6.9

D;D;D

REVEL

Benign

0.21

Sift

Benign

0.032

D;D;D

Sift4G

Benign

0.10

T;T;D

Polyphen

1.0

D;D;D

Vest4

0.19

MVP

0.52

MPC

0.74

ClinPred

0.52

GERP RS

4.6

Varity_R

0.25

gMVP

0.30

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