5-138329634-G-A

Variant names:

• chr5-138329634-G-A
• rs3734166
• NM_001790.5:c.208C>T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001790.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC25C	NM_001790.5	MANE Select	c.208C>T	p.Arg70Cys	missense	Exon 3 of 14	NP_001781.2
	CDC25C	NM_001287583.2		c.442C>T	p.Arg148Cys	missense	Exon 3 of 14	NP_001274512.1
	CDC25C	NM_001364026.1		c.442C>T	p.Arg148Cys	missense	Exon 3 of 13	NP_001350955.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC25C	ENST00000323760.11	TSL:1 MANE Select	c.208C>T	p.Arg70Cys	missense	Exon 3 of 14	ENSP00000321656.6
	CDC25C	ENST00000513970.5	TSL:2	c.208C>T	p.Arg70Cys	missense	Exon 3 of 14	ENSP00000424795.1
	CDC25C	ENST00000514555.5	TSL:5	c.208C>T	p.Arg70Cys	missense	Exon 2 of 12	ENSP00000425470.1

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

GnomAD2 exomes AF: 0.318 AC: 79910 AN: 251092 AF XY: 0.308

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 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

African (AFR) AF: 0.454 AC: 15026 AN: 33098

American (AMR) AF: 0.334 AC: 14885 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 10067 AN: 26006

East Asian (EAS) AF: 0.576 AC: 22794 AN: 39542

South Asian (SAS) AF: 0.197 AC: 16963 AN: 86006

European-Finnish (FIN) AF: 0.314 AC: 16734 AN: 53322

Middle Eastern (MID) AF: 0.366 AC: 2097 AN: 5734

European-Non Finnish (NFE) AF: 0.258 AC: 283932 AN: 1101368

Other (OTH) AF: 0.310 AC: 18561 AN: 59936

GnomAD4 genome AF: 0.342 AC: 51739 AN: 151408 Hom.: 9471 Cov.: 31 AF XY: 0.348 AC XY: 25703 AN XY: 73922

African (AFR) AF: 0.442 AC: 18235 AN: 41230

American (AMR) AF: 0.341 AC: 5168 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3466

East Asian (EAS) AF: 0.608 AC: 3146 AN: 5176

South Asian (SAS) AF: 0.212 AC: 1021 AN: 4810

European-Finnish (FIN) AF: 0.341 AC: 3541 AN: 10384

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18100 AN: 67884

Other (OTH) AF: 0.361 AC: 756 AN: 2092

Alfa AF: 0.302 Hom.: 28846

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 v4.9

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
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.000015	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.035	N
PhyloP100		-0.81
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.075
Sift	Benign	0.22	T
Sift4G	Uncertain	0.052	T
Polyphen		0.0030	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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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