dbSNP rs759190666: CCNK:p.Pro510Pro (chr14-99510569-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.1530A>C(p.Pro510Pro) 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 0.000024 ( 0 hom., cov: 8)

Exomes 𝑓: 0.0000041 ( 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: -1.82

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=-0.7).

BP6

Variant 14-99510569-A-C is Benign according to our data. Variant chr14-99510569-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 402508.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.82 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNK	NM_001099402.2	MANE Select	c.1530A>C	p.Pro510Pro	synonymous	Exon 11 of 11	NP_001092872.1	O75909-3
	CCDC85C	NM_001144995.2	MANE Select	c.*4677T>G		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.1530A>C	p.Pro510Pro	synonymous	Exon 11 of 11	ENSP00000374529.5	O75909-3
CCDC85C	ENST00000380243.9	TSL:5 MANE Select	c.*4677T>G		3_prime_UTR	Exon 6 of 6	ENSP00000369592.4	A6NKD9
CCNK	ENST00000555049.5	TSL:1	c.1117+3422A>C		intron	N/A	ENSP00000452307.1	G3V5E1

Frequencies

GnomAD3 genomes

AF:

0.0000240

AC:

AN:

41688

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:

0.0000438

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000211

AC:

AN:

66390

AF XY:

0.000232

show subpopulations

Gnomad AFR exome

AF:

0.000386

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000449

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000498

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000407

AC:

AN:

245632

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

134938

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6856

American (AMR)

AF:

0.00

AC:

AN:

17794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6142

East Asian (EAS)

AF:

0.00

AC:

AN:

10480

South Asian (SAS)

AF:

0.00

AC:

AN:

47530

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

872

European-Non Finnish (NFE)

AF:

0.00000755

AC:

AN:

132398

Other (OTH)

AF:

0.00

AC:

AN:

11956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000240

AC:

AN:

41688

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

19192

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:

9016

American (AMR)

AF:

0.00

AC:

AN:

3890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1310

East Asian (EAS)

AF:

0.00

AC:

AN:

1016

South Asian (SAS)

AF:

0.00

AC:

AN:

554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

116

European-Non Finnish (NFE)

AF:

0.0000438

AC:

AN:

22834

Other (OTH)

AF:

0.00

AC:

AN:

542

⚠️ 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: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.1

(source)

DANN

Benign

0.64

PhyloP100

-1.8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over