Variant 13-114235094-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001078645.3(CDC16):c.10G>A(p.Glu4Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000136 in 1,245,540 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: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CDC16
NM_001078645.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56

Variant links:

Genes affected

CDC16 (HGNC:1720): (cell division cycle 16) The protein encoded by this gene functions as a protein ubiquitin ligase and is a component of the multiprotein APC complex. The APC complex is a cyclin degradation system that governs exit from mitosis by targeting cell cycle proteins for degredation by the 26S proteasome. Each component protein of the APC complex is highly conserved among eukaryotic organisms. This protein, and other APC complex proteins, contain a tetratricopeptide repeat (TPR) domain; a protein domain that is often involved in protein-protein interactions and the assembly of multiprotein complexes. Multiple alternatively spliced transcript variants, encoding distinct proteins, have been identified. [provided by RefSeq, Jan 2016]

CDC16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019768268).

BS2

High AC in GnomAd at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC16	NM_001078645.3 linkuse as main transcript	c.10G>A	p.Glu4Lys	missense_variant	1/18	ENST00000356221.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC16	ENST00000356221.8 linkuse as main transcript	c.10G>A	p.Glu4Lys	missense_variant	1/18	1	NM_001078645.3	A1	Q13042-1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152110

Hom.:

Cov.:

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:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000680

AC:

AN:

5886

Hom.:

AF XY:

0.000576

AC XY:

AN XY:

3470

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000945

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000142

AC:

155

AN:

1093430

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

518500

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000341

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:

0.000160

Gnomad4 OTH exome

AF:

0.0000905

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74276

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:

0.000188

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.000122

AC:

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 submitter

clinical testing

Ambry Genetics

Mar 12, 2024

The c.10G>A (p.E4K) alteration is located in exon 1 (coding exon 1) of the CDC16 gene. This alteration results from a G to A substitution at nucleotide position 10, causing the glutamic acid (E) at amino acid position 4 to be replaced by a lysine (K). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;.

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

T;.;T

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.020

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.063

Sift

Benign

0.071

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.21

B;B;P

Vest4

0.19

MutPred

0.31

Loss of methylation at R7 (P = 0.1239);Loss of methylation at R7 (P = 0.1239);Loss of methylation at R7 (P = 0.1239);

MVP

0.20

MPC

1.3

ClinPred

0.28

GERP RS

4.2

Varity_R

0.36

gMVP

0.44

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over