14-99507088-C-T

Position:

chr14-99507088-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099402.2(CCNK):c.1058C>T(p.Pro353Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,188 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: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCNK
NM_001099402.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17300361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNK	NM_001099402.2 linkuse as main transcript	c.1058C>T	p.Pro353Leu	missense_variant	10/11	ENST00000389879.9	NP_001092872.1	O75909-3A0A024R6K1
CCDC85C	NM_001144995.2 linkuse as main transcript	c.*8158G>A		3_prime_UTR_variant	6/6	ENST00000380243.9	NP_001138467.1	A6NKD9
CCNK	XM_005268154.5 linkuse as main transcript	c.1058C>T	p.Pro353Leu	missense_variant	10/11		XP_005268211.1	O75909-3A0A024R6K1
CCNK	XM_047431839.1 linkuse as main transcript	c.1058C>T	p.Pro353Leu	missense_variant	11/12		XP_047287795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCNK	ENST00000389879.9 linkuse as main transcript	c.1058C>T	p.Pro353Leu	missense_variant	10/11	5	NM_001099402.2	ENSP00000374529.5	O75909-3
CCNK	ENST00000555049.5 linkuse as main transcript	c.1058C>T	p.Pro353Leu	missense_variant	10/11	1		ENSP00000452307.1	G3V5E1
CCDC85C	ENST00000380243 linkuse as main transcript	c.*8158G>A		3_prime_UTR_variant	6/6	5	NM_001144995.2	ENSP00000369592.4	A6NKD9
CCNK	ENST00000553865.1 linkuse as main transcript	n.4210C>T		non_coding_transcript_exon_variant	4/5	1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152188

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1456876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725192

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000756

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

Sep 04, 2024

The c.1058C>T (p.P353L) alteration is located in exon 10 (coding exon 9) of the CCNK gene. This alteration results from a C to T substitution at nucleotide position 1058, causing the proline (P) at amino acid position 353 to be replaced by a leucine (L). 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

0.066

BayesDel_addAF

Benign

-0.0080

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.27

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

0.016

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.079

MetaRNN

Benign

0.17

T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

0.69

N;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.10

Sift

Benign

0.079

T;T

Sift4G

Uncertain

0.056

T;T

Polyphen

0.0

B;.

Vest4

0.18

MVP

0.51

MPC

0.27

ClinPred

0.95

GERP RS

4.7

Varity_R

0.19

gMVP

0.11

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