14-99510268-T-A

Position:

• chr14-99510268-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099402.2(CCNK):​c.1229T>A​(p.Val410Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: CCNK NM_001099402.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14468712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNK	NM_001099402.2	c.1229T>A	p.Val410Glu	missense_variant	11/11	ENST00000389879.9	NP_001092872.1
CCDC85C	NM_001144995.2	c.*4978A>T		3_prime_UTR_variant	6/6	ENST00000380243.9	NP_001138467.1
CCNK	XM_005268154.5	c.1229T>A	p.Val410Glu	missense_variant	11/11		XP_005268211.1
CCNK	XM_047431839.1	c.1229T>A	p.Val410Glu	missense_variant	12/12		XP_047287795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNK	ENST00000389879.9	c.1229T>A	p.Val410Glu	missense_variant	11/11	5	NM_001099402.2	ENSP00000374529	P1
CCDC85C	ENST00000380243.9	c.*4978A>T		3_prime_UTR_variant	6/6	5	NM_001144995.2	ENSP00000369592	P1
CCNK	ENST00000555049.5	c.1117+3121T>A		intron_variant		1		ENSP00000452307
CCNK	ENST00000553865.1	n.4381T>A		non_coding_transcript_exon_variant	5/5	1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2024

The c.1229T>A (p.V410E) alteration is located in exon 11 (coding exon 10) of the CCNK gene. This alteration results from a T to A substitution at nucleotide position 1229, causing the valine (V) at amino acid position 410 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.022
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.36	T
Polyphen		0.089	B
Vest4		0.28
MutPred		0.36		Gain of catalytic residue at P413 (P = 0.001);
MVP		0.22
MPC		0.43
ClinPred		0.58	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.44
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-99976605;