chr5-138286053-C-G

Variant names:

• chr5-138286053-C-G
• NM_001790.5:c.1241G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001790.5(CDC25C):​c.1241G>C​(p.Gly414Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G414D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CDC25C NM_001790.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.28

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.981

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC25C	NM_001790.5	c.1241G>C	p.Gly414Ala	missense_variant	Exon 13 of 14	ENST00000323760.11	NP_001781.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC25C	ENST00000323760.11	c.1241G>C	p.Gly414Ala	missense_variant	Exon 13 of 14	1	NM_001790.5	ENSP00000321656.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461676 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D;.;.;D;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	.;D;.;D;D
M_CAP	Benign	0.083	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Pathogenic	3.5	H;.;.;H;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.3	D;D;D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.86
MutPred		0.95		Gain of catalytic residue at G414 (P = 0.0641);.;.;Gain of catalytic residue at G414 (P = 0.0641);.;
MVP		0.90
MPC		0.72
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.82
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-137621742;