rs3734166

chr5-138329634-G-Achr5-138329634-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809

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]

ACMG classification

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	UniProt
CDC25C	NM_001790.5	c.208C>T	p.Arg70Cys	missense_variant	3/14	ENST00000323760.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC25C	ENST00000323760.11	c.208C>T	p.Arg70Cys	missense_variant	3/14	1	NM_001790.5	P2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51713 AN: 151304 Hom.: 9465 Cov.: 31

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

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.: 30 AF XY: 0.275 AC XY: 198237 AN XY: 721834

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.: 31 AF XY: 0.348 AC XY: 25703 AN XY: 73922

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	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	14
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	N
MetaRNN	Benign	0.000015	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.035	N;N;N;.;.
MutationTaster	Benign	0.26	P;P;P;P;P;P;P
PrimateAI	Benign	0.20	T
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	T
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

Other links and lift over

dbSNP: rs3734166; hg19: chr5-137665323; COSMIC: COSV60398304; COSMIC: COSV60398304;