chr14-99510485-G-C

Variant names:

• chr14-99510485-G-C
• rs746815273
• NM_001099402.2:c.1446G>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.07
• Publications: 0 publications found

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]

ACMG classification

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
CCNK	NM_001099402.2	c.1446G>C	p.Pro482Pro	synonymous_variant	Exon 11 of 11	ENST00000389879.9	NP_001092872.1
CCDC85C	NM_001144995.2	c.*4761C>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000380243.9	NP_001138467.1
CCNK	XM_005268154.5	c.1446G>C	p.Pro482Pro	synonymous_variant	Exon 11 of 11		XP_005268211.1
CCNK	XM_047431839.1	c.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
CCNK	ENST00000389879.9	c.1446G>C	p.Pro482Pro	synonymous_variant	Exon 11 of 11	5	NM_001099402.2	ENSP00000374529.5
CCNK	ENST00000553865.1	n.4598G>C		non_coding_transcript_exon_variant	Exon 5 of 5	1
CCDC85C	ENST00000380243.9	c.*4761C>G		3_prime_UTR_variant	Exon 6 of 6	5	NM_001144995.2	ENSP00000369592.4
CCNK	ENST00000555049.5	c.1117+3338G>C		intron_variant	Intron 10 of 10	1		ENSP00000452307.1

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

⚠️ 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.

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

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

Other links and lift over

dbSNP: rs746815273; hg19: chr14-99976822;