9-96534038-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_033331.4(CDC14B):​c.835G>A​(p.Asp279Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,460,716 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: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CDC14B
NM_033331.4 missense

Scores

6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16
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 -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.34103078).
BS2
High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDC14BNM_033331.4 linkuse as main transcriptc.835G>A p.Asp279Asn missense_variant 9/14 ENST00000375241.6 NP_201588.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDC14BENST00000375241.6 linkuse as main transcriptc.835G>A p.Asp279Asn missense_variant 9/141 NM_033331.4 ENSP00000364389 A1O60729-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1460716
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
726618
show subpopulations
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:
0.00000900
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113

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 GeneticsJul 13, 2021The c.835G>A (p.D279N) alteration is located in exon 9 (coding exon 9) of the CDC14B gene. This alteration results from a G to A substitution at nucleotide position 835, causing the aspartic acid (D) at amino acid position 279 to be replaced by an asparagine (N). 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
0.076
BayesDel_addAF
Benign
-0.025
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.55
D;.;.;.
Eigen
Benign
0.043
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.90
D;D;D;D
M_CAP
Benign
0.045
D
MetaRNN
Benign
0.34
T;T;T;T
MetaSVM
Benign
-0.79
T
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-3.0
D;D;D;D
REVEL
Uncertain
0.33
Sift
Benign
0.093
T;T;T;T
Sift4G
Benign
0.086
T;T;T;T
Polyphen
0.062
B;B;.;.
Vest4
0.12
MVP
0.75
MPC
0.41
ClinPred
0.93
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.30
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs752429241; hg19: chr9-99296320; API