Genetic Variant CCNK:p.Pro508Pro (chr14-99510563-A-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001099402.2(CCNK):c.1524A>C(p.Pro508Pro) 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 (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., cov: 6)

Exomes 𝑓: 0.000075 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCNK
NM_001099402.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.896

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 14-99510563-A-C is Benign according to our data. Variant chr14-99510563-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 402507.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.896 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099402.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNK	NM_001099402.2	MANE Select	c.1524A>C	p.Pro508Pro	synonymous	Exon 11 of 11	NP_001092872.1
	CCDC85C	NM_001144995.2	MANE Select	c.*4683T>G		3_prime_UTR	Exon 6 of 6	NP_001138467.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CCNK	ENST00000389879.9	TSL:5 MANE Select	c.1524A>C	p.Pro508Pro	synonymous	Exon 11 of 11	ENSP00000374529.5
CCNK	ENST00000553865.1	TSL:1	n.4676A>C		non_coding_transcript_exon	Exon 5 of 5
CCDC85C	ENST00000380243.9	TSL:5 MANE Select	c.*4683T>G		3_prime_UTR	Exon 6 of 6	ENSP00000369592.4

Frequencies

GnomAD3 genomes

AF:

0.0000632

AC:

AN:

31668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000114

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000377

AC:

AN:

60938

AF XY:

0.000408

show subpopulations

Gnomad AFR exome

AF:

0.000210

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000483

Gnomad EAS exome

AF:

0.000138

Gnomad FIN exome

AF:

0.00178

Gnomad NFE exome

AF:

0.000851

Gnomad OTH exome

AF:

0.000503

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000753

AC:

AN:

199280

Hom.:

Cov.:

AF XY:

0.0000634

AC XY:

AN XY:

110442

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

5708

American (AMR)

AF:

0.00

AC:

AN:

15038

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4922

East Asian (EAS)

AF:

0.000131

AC:

AN:

7650

South Asian (SAS)

AF:

0.0000489

AC:

AN:

40894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

680

European-Non Finnish (NFE)

AF:

0.000114

AC:

AN:

105576

Other (OTH)

AF:

0.00

AC:

AN:

9652

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.262

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000632

AC:

AN:

31668

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

14684

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

6738

American (AMR)

AF:

0.00

AC:

AN:

2912

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1012

East Asian (EAS)

AF:

0.00

AC:

AN:

776

South Asian (SAS)

AF:

0.00

AC:

AN:

428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000114

AC:

AN:

17572

Other (OTH)

AF:

0.00

AC:

AN:

420

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC data poor quality. Silent variant no splice impact

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.4

(source)

DANN

Benign

0.69

PhyloP100

-0.90

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over