5-138285763-T-C

Position:

• chr5-138285763-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000323760.11(CDC25C):​c.1351A>G​(p.Ser451Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CDC25C ENST00000323760.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13948366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC25C	NM_001790.5	c.1351A>G	p.Ser451Gly	missense_variant	14/14	ENST00000323760.11	NP_001781.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC25C	ENST00000323760.11	c.1351A>G	p.Ser451Gly	missense_variant	14/14	1	NM_001790.5	ENSP00000321656	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 11, 2023

The c.1351A>G (p.S451G) alteration is located in exon 14 (coding exon 13) of the CDC25C gene. This alteration results from a A to G substitution at nucleotide position 1351, causing the serine (S) at amino acid position 451 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.80	D;.;.;D;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.80	.;T;.;T;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M;.;.;M;.
MutationTaster	Benign	0.95	D;D;D;D;D;D;D
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.1	D;D;D;D;D
REVEL	Benign	0.065
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.025	D;D;D;D;D
Polyphen		0.077	B;B;B;B;B
Vest4		0.31
MutPred		0.20		Loss of phosphorylation at S451 (P = 0.0239);.;.;Loss of phosphorylation at S451 (P = 0.0239);.;
MVP		0.57
MPC		0.20
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.24
gMVP		0.53

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: chr5-137621452;