chr14-99510485-G-C

Variant summary

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

The NM_001099402.2(CCNK):​c.1446G>C​(p.Pro482Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000098 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CCNK
NM_001099402.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

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]
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]

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=-0.92).
BP6
Variant 14-99510485-G-C is Benign according to our data. Variant chr14-99510485-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 402506.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.07 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCNKNM_001099402.2 linkc.1446G>C p.Pro482Pro synonymous_variant Exon 11 of 11 ENST00000389879.9 NP_001092872.1 O75909-3A0A024R6K1
CCDC85CNM_001144995.2 linkc.*4761C>G 3_prime_UTR_variant Exon 6 of 6 ENST00000380243.9 NP_001138467.1 A6NKD9
CCNKXM_005268154.5 linkc.1446G>C p.Pro482Pro synonymous_variant Exon 11 of 11 XP_005268211.1 O75909-3A0A024R6K1
CCNKXM_047431839.1 linkc.1446G>C p.Pro482Pro synonymous_variant Exon 12 of 12 XP_047287795.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCNKENST00000389879.9 linkc.1446G>C p.Pro482Pro synonymous_variant Exon 11 of 11 5 NM_001099402.2 ENSP00000374529.5 O75909-3
CCNKENST00000553865.1 linkn.4598G>C non_coding_transcript_exon_variant Exon 5 of 5 1
CCDC85CENST00000380243.9 linkc.*4761C>G 3_prime_UTR_variant Exon 6 of 6 5 NM_001144995.2 ENSP00000369592.4 A6NKD9
CCNKENST00000555049.5 linkc.1117+3338G>C intron_variant Intron 10 of 10 1 ENSP00000452307.1 G3V5E1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
13972
Hom.:
0
Cov.:
0
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000979
AC:
6
AN:
613058
Hom.:
0
Cov.:
17
AF XY:
0.00000649
AC XY:
2
AN XY:
308268
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:
0
AN:
14394
American (AMR)
AF:
0.00
AC:
0
AN:
22386
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
10326
East Asian (EAS)
AF:
0.00
AC:
0
AN:
9482
South Asian (SAS)
AF:
0.00
AC:
0
AN:
42182
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
17394
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1606
European-Non Finnish (NFE)
AF:
0.0000127
AC:
6
AN:
472098
Other (OTH)
AF:
0.00
AC:
0
AN:
23190
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.007278), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.383
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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: AC0
AF:
0.00
AC:
0
AN:
13972
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
6702
African (AFR)
AF:
0.00
AC:
0
AN:
3278
American (AMR)
AF:
0.00
AC:
0
AN:
1000
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
406
East Asian (EAS)
AF:
0.00
AC:
0
AN:
388
South Asian (SAS)
AF:
0.00
AC:
0
AN:
438
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
656
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
14
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
7466
Other (OTH)
AF:
0.00
AC:
0
AN:
220
Alfa
AF:
0.00
Hom.:
0

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: same variant as above, silent no splice impact -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.31
DANN
Benign
0.50
PhyloP100
-1.1
Mutation Taster
=97/3
polymorphism

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

Other links and lift over

dbSNP: rs746815273; hg19: chr14-99976822; API