Variant 5-138329634-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001790.5(CDC25C):c.208C>T(p.Arg70Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,601,042 control chromosomes in the GnomAD database, including 69,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 9471 hom., cov: 31)

Exomes 𝑓: 0.28 ( 60037 hom. )

Consequence

CDC25C
NM_001790.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.809

Variant links:

Genes affected

CDC25C (HGNC:1727): (cell division cycle 25C) This gene encodes a conserved protein that plays a key role in the regulation of cell division. The encoded protein directs dephosphorylation of cyclin B-bound CDC2 and triggers entry into mitosis. It also suppresses p53-induced growth arrest. Multiple alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Dec 2015]

CDC25C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5131643E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC25C	NM_001790.5 linkuse as main transcript	c.208C>T	p.Arg70Cys	missense_variant	3/14	ENST00000323760.11	NP_001781.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC25C	ENST00000323760.11 linkuse as main transcript	c.208C>T	p.Arg70Cys	missense_variant	3/14	1	NM_001790.5	ENSP00000321656	P2	P30307-1

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

51713

AN:

151304

Hom.:

9465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.607

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.357

GnomAD3 exomes

AF:

0.318

AC:

79910

AN:

251092

Hom.:

14056

AF XY:

0.308

AC XY:

41869

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.452

Gnomad AMR exome

AF:

0.333

Gnomad ASJ exome

AF:

0.384

Gnomad EAS exome

AF:

0.606

Gnomad SAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.331

GnomAD4 exome

AF:

0.277

AC:

401059

AN:

1449634

Hom.:

60037

Cov.:

AF XY:

0.275

AC XY:

198237

AN XY:

721834

show subpopulations

Gnomad4 AFR exome

AF:

0.454

Gnomad4 AMR exome

AF:

0.334

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.576

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.314

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.310

GnomAD4 genome

AF:

0.342

AC:

51739

AN:

151408

Hom.:

9471

Cov.:

AF XY:

0.348

AC XY:

25703

AN XY:

73922

show subpopulations

Gnomad4 AFR

AF:

0.442

Gnomad4 AMR

AF:

0.341

Gnomad4 ASJ

AF:

0.370

Gnomad4 EAS

AF:

0.608

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.341

Gnomad4 NFE

AF:

0.267

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.295

Hom.:

17974

Bravo

AF:

0.355

ESP6500AA

AF:

0.446

AC:

1964

ESP6500EA

AF:

0.278

AC:

2388

ExAC

AF:

0.317

AC:

38539

Asia WGS

AF:

0.388

AC:

1352

AN:

3478

EpiCase

AF:

0.294

EpiControl

AF:

0.301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;T;.;.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.70

.;T;T;T;T

MetaRNN

Benign

0.000015

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.035

N;N;N;.;.

MutationTaster

Benign

0.26

P;P;P;P;P;P;P

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.23

N;N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.22

T;T;T;T;T

Sift4G

Uncertain

0.052

T;T;T;D;T

Polyphen

0.0030

B;B;B;.;.

Vest4

0.057

MPC

0.23

ClinPred

0.022

GERP RS

-0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.046

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over