14-99502863-C-G

Position:

chr14-99502863-C-G

Variant summary

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

The NM_001099402.2(CCNK):c.890C>G(p.Ser297Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CCNK
NM_001099402.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22

Variant links:

Genes affected

CCNK (HGNC:1596): (cyclin K) The protein encoded by this gene is a member of the transcription cyclin family. These cyclins may regulate transcription through their association with and activation of cyclin-dependent kinases (CDK) that phosphorylate the C-terminal domain (CTD) of the large subunit of RNA polymerase II. This gene product may play a dual role in regulating CDK and RNA polymerase II activities. [provided by RefSeq, Jul 2008]

CCNK links:

CCDC85C (HGNC:35459): (coiled-coil domain containing 85C) Predicted to be involved in cerebral cortex development. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

CCDC85C links:

CCNK (HGNC:):

CCNK links:

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=0.215875).

BS2

High AC in GnomAdExome4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNK	NM_001099402.2 linkuse as main transcript	c.890C>G	p.Ser297Cys	missense_variant	8/11	ENST00000389879.9	NP_001092872.1	O75909-3A0A024R6K1
CCDC85C	NM_001144995.2 linkuse as main transcript	c.*12383G>C		3_prime_UTR_variant	6/6	ENST00000380243.9	NP_001138467.1	A6NKD9
CCNK	XM_005268154.5 linkuse as main transcript	c.890C>G	p.Ser297Cys	missense_variant	8/11		XP_005268211.1	O75909-3A0A024R6K1
CCNK	XM_047431839.1 linkuse as main transcript	c.890C>G	p.Ser297Cys	missense_variant	9/12		XP_047287795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCNK	ENST00000389879.9 linkuse as main transcript	c.890C>G	p.Ser297Cys	missense_variant	8/11	5	NM_001099402.2	ENSP00000374529.5	O75909-3
CCNK	ENST00000555049.5 linkuse as main transcript	c.890C>G	p.Ser297Cys	missense_variant	8/11	1		ENSP00000452307.1	G3V5E1
CCDC85C	ENST00000380243 linkuse as main transcript	c.*12383G>C		3_prime_UTR_variant	6/6	5	NM_001144995.2	ENSP00000369592.4	A6NKD9
CCNK	ENST00000553865.1 linkuse as main transcript	n.3416C>G		non_coding_transcript_exon_variant	3/5	1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248546

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134786

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:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461212

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726784

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:

0.0000306

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000825

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

Oct 01, 2024

The c.890C>G (p.S297C) alteration is located in exon 8 (coding exon 7) of the CCNK gene. This alteration results from a C to G substitution at nucleotide position 890, causing the serine (S) at amino acid position 297 to be replaced by a cysteine (C). 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

0.099

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.17

T;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.22

T;T

MetaSVM

Uncertain

0.16

MutationAssessor

Benign

1.6

L;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.23

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.040

D;D

Polyphen

0.70

P;.

Vest4

0.21

MutPred

0.34

Loss of phosphorylation at S297 (P = 0.0038);Loss of phosphorylation at S297 (P = 0.0038);

MVP

0.57

MPC

0.26

ClinPred

0.59

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.089

gMVP

0.19

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