rs35385659

Variant names:

• chr1-100499154-C-A
• rs35385659
• NM_003672.4:c.1647C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 2 publications found

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]

CDC14A Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic deafness 105

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal recessive nonsyndromic hearing loss 32

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia
• hearing impairment and infertile male syndrome

  Inheritance: AR Classification: STRONG Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000228086 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 rank	MANE	Protein	UniProt
CDC14A	NM_003672.4	c.1647C>A	p.Ser549Arg	missense_variant	Exon 15 of 16	ENST00000336454.5	NP_003663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC14A	ENST00000336454.5	c.1647C>A	p.Ser549Arg	missense_variant	Exon 15 of 16	1	NM_003672.4	ENSP00000336739.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 7

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
PhyloP100		1.5
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
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs35385659; hg19: chr1-100964710;