14-99510485-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001099402.2(CCNK):​c.1446G>T​(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.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: CCNK NM_001099402.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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>T	p.Pro482Pro	synonymous_variant	Exon 11 of 11	ENST00000389879.9	NP_001092872.1
CCDC85C	NM_001144995.2	c.*4761C>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000380243.9	NP_001138467.1
CCNK	XM_005268154.5	c.1446G>T	p.Pro482Pro	synonymous_variant	Exon 11 of 11		XP_005268211.1
CCNK	XM_047431839.1	c.1446G>T	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>T	p.Pro482Pro	synonymous_variant	Exon 11 of 11	5	NM_001099402.2	ENSP00000374529.5
CCDC85C	ENST00000380243	c.*4761C>A		3_prime_UTR_variant	Exon 6 of 6	5	NM_001144995.2	ENSP00000369592.4
CCNK	ENST00000555049.5	c.1117+3338G>T		intron_variant	Intron 10 of 10	1		ENSP00000452307.1
CCNK	ENST00000553865.1	n.4598G>T		non_coding_transcript_exon_variant	Exon 5 of 5	1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000326 AC: 2 AN: 613060 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 308268

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000105

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000431

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs746815273; hg19: chr14-99976822;