1-100468020-T-C

Variant names:

• chr1-100468020-T-C
• rs17122597
• NM_003672.4:c.903T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003672.4(CDC14A):​c.903T>C​(p.His301His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,613,124 control chromosomes in the GnomAD database, including 1,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (891 hom., cov: 33)
  • Exomes 𝑓: 0.0061 (729 hom.)
• Consequence: CDC14A NM_003672.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.00

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]

ENSG00000228086 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-100468020-T-C is Benign according to our data. Variant chr1-100468020-T-C is described in ClinVar as [Benign]. Clinvar id is 517534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC14A	NM_003672.4	c.903T>C	p.His301His	synonymous_variant	Exon 10 of 16	ENST00000336454.5	NP_003663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC14A	ENST00000336454.5	c.903T>C	p.His301His	synonymous_variant	Exon 10 of 16	1	NM_003672.4	ENSP00000336739.3

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8881 AN: 152148 Hom.: 886 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.0420

GnomAD3 exomes AF: 0.0154 AC: 3857 AN: 249854 Hom.: 360 AF XY: 0.0111 AC XY: 1494 AN XY: 135084

Gnomad AFR exome AF: 0.206

Gnomad AMR exome AF: 0.00921

Gnomad ASJ exome AF: 0.00687

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000461

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000839

Gnomad OTH exome AF: 0.00776

GnomAD4 exome AF: 0.00608 AC: 8880 AN: 1460858 Hom.: 729 Cov.: 31 AF XY: 0.00530 AC XY: 3850 AN XY: 726746

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.00521

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000616

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.000447

Gnomad4 OTH exome AF: 0.0135

GnomAD4 genome AF: 0.0585 AC: 8912 AN: 152266 Hom.: 891 Cov.: 33 AF XY: 0.0567 AC XY: 4220 AN XY: 74472

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0214 Hom.: 150

Bravo AF: 0.0655

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.00125

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.His301His in exon 10 of CDC14A: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 20.33% (2115/10404 ) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs17122597). -

Oct 05, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:2

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.13
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17122597; hg19: chr1-100933576;