rs35385659

Positions:

• chr1-100499154-C-A
• chr1-100499154-C-T

Variant summary

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

The NM_003672.4(CDC14A):​c.1647C>A​(p.Ser549Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Synonymous variant affecting the same amino acid position (i.e. S549S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC14A NM_003672.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

Genes affected

CDC14A (HGNC:1718): (cell division cycle 14A) The protein encoded by this gene is a member of the dual specificity protein tyrosine phosphatase family. It is highly similar to Saccharomyces cerevisiae Cdc14, a protein tyrosine phosphatase involved in the exit of cell mitosis and initiation of DNA replication, suggesting a role in cell cycle control. This protein has been shown to interact with, and dephosphorylate tumor suppressor protein p53, and is thought to regulate the function of p53. Alternative splicing of this gene results in several transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

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=0.09071085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC14A	NM_003672.4	c.1647C>A	p.Ser549Arg	missense_variant	15/16	ENST00000336454.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC14A	ENST00000336454.5	c.1647C>A	p.Ser549Arg	missense_variant	15/16	1	NM_003672.4	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	.;.;.;.;T;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.76	T;T;T;T;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.091	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	.;.;.;M;M;M
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	.;.;.;N;N;.
REVEL	Benign	0.029
Sift	Benign	0.23	.;.;.;T;D;.
Sift4G	Benign	0.21	T;.;.;T;D;.
Polyphen		0.0010	.;.;.;B;B;.
Vest4		0.34
MutPred		0.22		.;.;.;Loss of phosphorylation at S549 (P = 0.0231);Loss of phosphorylation at S549 (P = 0.0231);Loss of phosphorylation at S549 (P = 0.0231);
MVP		0.58
MPC		0.22
ClinPred		0.53	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.076
gMVP		0.56

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

LitVar

Other links and lift over

dbSNP: rs35385659; hg19: chr1-100964710;