9-96503770-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_033331.4(CDC14B):ā€‹c.1480A>Gā€‹(p.Lys494Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000136 in 1,613,944 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000079 ( 0 hom., cov: 32)
Exomes š‘“: 0.00014 ( 0 hom. )

Consequence

CDC14B
NM_033331.4 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87
Variant links:
Genes affected
CDC14B (HGNC:1719): (cell division cycle 14B) The protein encoded by this gene is a member of the dual specificity protein tyrosine phosphatase family. This protein is highly similar to Saccharomyces cerevisiae Cdc14, a protein tyrosine phosphatase involved in the exit of cell mitosis and initiation of DNA replication, which suggests the role in cell cycle control. This protein has been shown to interact with and dephosphorylates tumor suppressor protein p53, and is thought to regulate the function of p53. Alternative splice of this gene results in 3 transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1528554).
BS2
High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDC14BNM_033331.4 linkuse as main transcriptc.1480A>G p.Lys494Glu missense_variant 14/14 ENST00000375241.6 NP_201588.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDC14BENST00000375241.6 linkuse as main transcriptc.1480A>G p.Lys494Glu missense_variant 14/141 NM_033331.4 ENSP00000364389 A1O60729-1

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152200
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251150
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000792
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000142
AC:
207
AN:
1461744
Hom.:
0
Cov.:
29
AF XY:
0.000160
AC XY:
116
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000164
Gnomad4 OTH exome
AF:
0.000215
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000154
Hom.:
0
Bravo
AF:
0.000125
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 10, 2023The c.1480A>G (p.K494E) alteration is located in exon 14 (coding exon 14) of the CDC14B gene. This alteration results from a A to G substitution at nucleotide position 1480, causing the lysine (K) at amino acid position 494 to be replaced by a glutamic acid (E). 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
0.16
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Uncertain
0.10
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.037
T;.;.
Eigen
Benign
-0.065
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.76
T;T;T
M_CAP
Benign
0.073
D
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Benign
0.69
N;.;.
MutationTaster
Benign
1.0
D;D;N;N;N
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.53
N;N;N
REVEL
Uncertain
0.44
Sift
Uncertain
0.029
D;T;T
Sift4G
Benign
0.32
T;D;T
Polyphen
0.61
P;B;.
Vest4
0.27
MVP
0.93
MPC
0.59
ClinPred
0.10
T
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.43

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373515398; hg19: chr9-99266052; API