Variant 1-43361123-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001255.3(CDC20):c.1081G>A(p.Val361Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0069 in 1,614,008 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 70 hom. )

Consequence

CDC20
NM_001255.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.91

Variant links:

Genes affected

CDC20 (HGNC:1723): (cell division cycle 20) CDC20 appears to act as a regulatory protein interacting with several other proteins at multiple points in the cell cycle. It is required for two microtubule-dependent processes, nuclear movement prior to anaphase and chromosome separation. [provided by RefSeq, Jul 2008]

CDC20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01017648).

BP6

Variant 1-43361123-G-A is Benign according to our data. Variant chr1-43361123-G-A is described in ClinVar as [Benign]. Clinvar id is 770844.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00506 (770/152196) while in subpopulation SAS AF= 0.0201 (97/4820). AF 95% confidence interval is 0.0169. There are 8 homozygotes in gnomad4. There are 400 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC20	NM_001255.3 linkuse as main transcript	c.1081G>A	p.Val361Ile	missense_variant	9/11	ENST00000310955.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CDC20	ENST00000310955.11 linkuse as main transcript	c.1081G>A	p.Val361Ile	missense_variant	9/11	1	NM_001255.3	P1
CDC20	ENST00000372462.1 linkuse as main transcript	c.1081G>A	p.Val361Ile	missense_variant	8/10	1		P1
CDC20	ENST00000482046.1 linkuse as main transcript	n.66G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00507

AC:

771

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00654

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00733

AC:

1843

AN:

251384

Hom.:

AF XY:

0.00808

AC XY:

1098

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00338

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0186

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.00745

Gnomad OTH exome

AF:

0.00668

GnomAD4 exome

AF:

0.00709

AC:

10371

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00744

AC XY:

5413

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.00386

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0179

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.00677

Gnomad4 OTH exome

AF:

0.00704

GnomAD4 genome

AF:

0.00506

AC:

770

AN:

152196

Hom.:

Cov.:

AF XY:

0.00537

AC XY:

400

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00169

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0201

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.00654

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00616

Hom.:

Bravo

AF:

0.00398

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.00787

AC:

956

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.084

T;T

Eigen

Benign

-0.0051

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.90

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.11

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.66

N;N

REVEL

Benign

0.080

Sift

Benign

0.10

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.24

B;B

Vest4

0.21

MVP

0.72

MPC

0.30

ClinPred

0.0091

GERP RS

5.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.8

Varity_R

0.14

gMVP

0.080

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