Variant 14-99500849-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001099402.2(CCNK):c.495A>T(p.Leu165=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,548,782 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0038 ( 14 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 88 hom. )

Consequence

CCNK
NM_001099402.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.20

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 14-99500849-A-T is Benign according to our data. Variant chr14-99500849-A-T is described in ClinVar as [Benign]. Clinvar id is 3039124.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.2 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00384 (585/152384) while in subpopulation AMR AF= 0.0238 (365/15304). AF 95% confidence interval is 0.0218. There are 14 homozygotes in gnomad4. There are 337 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 585 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCNK	NM_001099402.2 linkuse as main transcript	c.495A>T	p.Leu165=	synonymous_variant	5/11	ENST00000389879.9	NP_001092872.1
CCDC85C	NM_001144995.2 linkuse as main transcript	c.*14397T>A		3_prime_UTR_variant	6/6	ENST00000380243.9	NP_001138467.1
CCNK	XM_005268154.5 linkuse as main transcript	c.495A>T	p.Leu165=	synonymous_variant	5/11		XP_005268211.1
CCNK	XM_047431839.1 linkuse as main transcript	c.495A>T	p.Leu165=	synonymous_variant	6/12		XP_047287795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNK	ENST00000389879.9 linkuse as main transcript	c.495A>T	p.Leu165=	synonymous_variant	5/11	5	NM_001099402.2	ENSP00000374529	P1	O75909-3
CCDC85C	ENST00000380243.9 linkuse as main transcript	c.*14397T>A		3_prime_UTR_variant	6/6	5	NM_001144995.2	ENSP00000369592	P1

Frequencies

GnomAD3 genomes

AF:

0.00386

AC:

587

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.0192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00902

AC:

1464

AN:

162368

Hom.:

AF XY:

0.00741

AC XY:

634

AN XY:

85550

show subpopulations

Gnomad AFR exome

AF:

0.000324

Gnomad AMR exome

AF:

0.0464

Gnomad ASJ exome

AF:

0.00566

Gnomad EAS exome

AF:

0.0157

Gnomad SAS exome

AF:

0.000242

Gnomad FIN exome

AF:

0.00418

Gnomad NFE exome

AF:

0.000422

Gnomad OTH exome

AF:

0.00536

GnomAD4 exome

AF:

0.00268

AC:

3744

AN:

1396398

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

1734

AN XY:

689562

show subpopulations

Gnomad4 AFR exome

AF:

0.000346

Gnomad4 AMR exome

AF:

0.0429

Gnomad4 ASJ exome

AF:

0.00423

Gnomad4 EAS exome

AF:

0.0415

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.00454

Gnomad4 NFE exome

AF:

0.000190

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00384

AC:

585

AN:

152384

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

337

AN XY:

74526

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.0238

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.0195

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00367

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00529

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CCNK-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 30, 2019

This variant is classified as 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

-0.60

CADD

Benign

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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