Genetic Variant CCNK:p.Pro482Pro (chr14-99510485-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_001099402.2(CCNK):c.1446G>A(p.Pro482Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P482P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

CCNK
NM_001099402.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=-1.07 with no splicing effect.

BS2

High AC in GnomAd4 at 15 Unknown,AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNK	NM_001099402.2	MANE Select	c.1446G>A	p.Pro482Pro	synonymous	Exon 11 of 11	NP_001092872.1	O75909-3
	CCDC85C	NM_001144995.2	MANE Select	c.*4761C>T		3_prime_UTR	Exon 6 of 6	NP_001138467.1	A6NKD9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCNK	ENST00000389879.9	TSL:5 MANE Select	c.1446G>A	p.Pro482Pro	synonymous	Exon 11 of 11	ENSP00000374529.5	O75909-3
CCDC85C	ENST00000380243.9	TSL:5 MANE Select	c.*4761C>T		3_prime_UTR	Exon 6 of 6	ENSP00000369592.4	A6NKD9
CCNK	ENST00000555049.5	TSL:1	c.1117+3338G>A		intron	N/A	ENSP00000452307.1	G3V5E1

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

AN:

13972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0150

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

GnomAD2 exomes

AF:

0.000128

AC:

AN:

101400

AF XY:

0.000146

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000577

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000281

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000587

AC:

AN:

613054

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

308268

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14394

American (AMR)

AF:

0.00116

AC:

AN:

22386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10326

East Asian (EAS)

AF:

0.00

AC:

AN:

9482

South Asian (SAS)

AF:

0.00

AC:

AN:

42182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17394

Middle Eastern (MID)

AF:

0.000623

AC:

AN:

1606

European-Non Finnish (NFE)

AF:

0.0000106

AC:

AN:

472094

Other (OTH)

AF:

0.000172

AC:

AN:

23190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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

AF:

0.00107

AC:

AN:

13978

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

AN XY:

6704

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3278

American (AMR)

AF:

0.0150

AC:

AN:

1002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

406

East Asian (EAS)

AF:

0.00

AC:

AN:

388

South Asian (SAS)

AF:

0.00

AC:

AN:

438

European-Finnish (FIN)

AF:

0.00

AC:

AN:

656

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

7468

Other (OTH)

AF:

0.00

AC:

AN:

222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.7

(source)

DANN

Benign

0.58

PhyloP100

-1.1

Mutation Taster

=97/3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over