14-99510160-G-A

Position:

chr14-99510160-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001099402.2(CCNK):c.1121G>A(p.Arg374Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000295 in 1,595,706 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

CCNK
NM_001099402.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCNK	NM_001099402.2 linkuse as main transcript	c.1121G>A	p.Arg374Gln	missense_variant	11/11	ENST00000389879.9
CCDC85C	NM_001144995.2 linkuse as main transcript	c.*5086C>T		3_prime_UTR_variant	6/6	ENST00000380243.9
CCNK	XM_005268154.5 linkuse as main transcript	c.1121G>A	p.Arg374Gln	missense_variant	11/11
CCNK	XM_047431839.1 linkuse as main transcript	c.1121G>A	p.Arg374Gln	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCNK	ENST00000389879.9 linkuse as main transcript	c.1121G>A	p.Arg374Gln	missense_variant	11/11	5	NM_001099402.2	P1	O75909-3
CCDC85C	ENST00000380243.9 linkuse as main transcript	c.*5086C>T		3_prime_UTR_variant	6/6	5	NM_001144995.2	P1
CCNK	ENST00000555049.5 linkuse as main transcript	c.1117+3013G>A		intron_variant		1
CCNK	ENST00000553865.1 linkuse as main transcript	n.4273G>A		non_coding_transcript_exon_variant	5/5	1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000364

AC:

AN:

220050

Hom.:

AF XY:

0.0000413

AC XY:

AN XY:

120998

show subpopulations

Gnomad AFR exome

AF:

0.0000792

Gnomad AMR exome

AF:

0.0000612

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:

0.0000510

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000305

AC:

AN:

1443624

Hom.:

Cov.:

AF XY:

0.0000307

AC XY:

AN XY:

717146

show subpopulations

Gnomad4 AFR exome

AF:

0.0000602

Gnomad4 AMR exome

AF:

0.0000461

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000343

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000302

ExAC

AF:

0.0000581

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Aug 02, 2022

The c.1121G>A (p.R374Q) alteration is located in exon 11 (coding exon 10) of the CCNK gene. This alteration results from a G to A substitution at nucleotide position 1121, causing the arginine (R) at amino acid position 374 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.10

Eigen_PC

Benign

0.054

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.019

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.66

REVEL

Benign

0.029

Sift

Benign

0.049

Sift4G

Benign

0.69

Polyphen

0.35

Vest4

0.27

MutPred

0.26

Gain of catalytic residue at P370 (P = 5e-04);

MVP

0.34

MPC

0.31

ClinPred

0.061

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.089

gMVP

0.086

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: 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