Variant 14-99510281-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001099402.2(CCNK):c.1242G>A(p.Pro414=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00045 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

CCNK
NM_001099402.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.17

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 14-99510281-G-A is Benign according to our data. Variant chr14-99510281-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3049684.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.17 with no splicing effect.

BS2

High AC in GnomAd4 at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCNK	NM_001099402.2 linkuse as main transcript	c.1242G>A	p.Pro414=	synonymous_variant	11/11	ENST00000389879.9	NP_001092872.1
CCDC85C	NM_001144995.2 linkuse as main transcript	c.*4965C>T		3_prime_UTR_variant	6/6	ENST00000380243.9	NP_001138467.1
CCNK	XM_005268154.5 linkuse as main transcript	c.1242G>A	p.Pro414=	synonymous_variant	11/11		XP_005268211.1
CCNK	XM_047431839.1 linkuse as main transcript	c.1242G>A	p.Pro414=	synonymous_variant	12/12		XP_047287795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNK	ENST00000389879.9 linkuse as main transcript	c.1242G>A	p.Pro414=	synonymous_variant	11/11	5	NM_001099402.2	ENSP00000374529	P1	O75909-3
CCDC85C	ENST00000380243.9 linkuse as main transcript	c.*4965C>T		3_prime_UTR_variant	6/6	5	NM_001144995.2	ENSP00000369592	P1
CCNK	ENST00000555049.5 linkuse as main transcript	c.1117+3134G>A		intron_variant		1		ENSP00000452307
CCNK	ENST00000553865.1 linkuse as main transcript	n.4394G>A		non_coding_transcript_exon_variant	5/5	1

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

AN:

46644

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000319

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0217

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000885

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000531

AC:

AN:

143078

Hom.:

AF XY:

0.000497

AC XY:

AN XY:

80494

show subpopulations

Gnomad AFR exome

AF:

0.000137

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000225

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00425

Gnomad NFE exome

AF:

0.000418

Gnomad OTH exome

AF:

0.00122

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000451

AC:

270

AN:

598996

Hom.:

Cov.:

AF XY:

0.000449

AC XY:

136

AN XY:

303230

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:

0.0000219

Gnomad4 FIN exome

AF:

0.00604

Gnomad4 NFE exome

AF:

0.000284

Gnomad4 OTH exome

AF:

0.000616

GnomAD4 genome

AF:

0.00133

AC:

AN:

46644

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

AN XY:

21998

show subpopulations

Gnomad4 AFR

AF:

0.000258

Gnomad4 AMR

AF:

0.000319

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0217

Gnomad4 NFE

AF:

0.000885

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000857

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CCNK-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 27, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.51

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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