Genetic Variant NM_001287135.2:c.962T>C (chr7-90984162-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001287135.2(CDK14):c.962T>C(p.Ile321Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CDK14
NM_001287135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46

Publications

0 publications found

Variant links:

Genes affected

CDK14 (HGNC:8883): (cyclin dependent kinase 14) Enables cyclin binding activity and cyclin-dependent protein serine/threonine kinase activity. Involved in G2/M transition of mitotic cell cycle and regulation of canonical Wnt signaling pathway. Located in cytosol; nucleoplasm; and plasma membrane. Part of cytoplasmic cyclin-dependent protein kinase holoenzyme complex. [provided by Alliance of Genome Resources, Apr 2022]

CDK14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.895

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK14	NM_001287135.2 link	c.962T>C	p.Ile321Thr	missense_variant	Exon 10 of 15	ENST00000380050.8	NP_001274064.1	O94921-1
CDK14	NM_012395.3 link	c.908T>C	p.Ile303Thr	missense_variant	Exon 9 of 14		NP_036527.1	O94921-2
CDK14	NM_001287136.1 link	c.824T>C	p.Ile275Thr	missense_variant	Exon 9 of 14		NP_001274065.1	O94921-3
CDK14	NM_001287137.1 link	c.575T>C	p.Ile192Thr	missense_variant	Exon 8 of 13		NP_001274066.1	O94921E7EUK8B4DK59

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDK14	ENST00000380050.8 link	c.962T>C	p.Ile321Thr	missense_variant	Exon 10 of 15	1	NM_001287135.2	ENSP00000369390.3	O94921-1
CDK14	ENST00000265741.7 link	c.908T>C	p.Ile303Thr	missense_variant	Exon 9 of 14	1		ENSP00000265741.3	O94921-2
CDK14	ENST00000406263.5 link	c.824T>C	p.Ile275Thr	missense_variant	Exon 9 of 14	1		ENSP00000385034.1	O94921-3
CDK14	ENST00000436577.3 link	c.575T>C	p.Ile192Thr	missense_variant	Exon 8 of 13	2		ENSP00000398936.2	E7EUK8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457070

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33380

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

86140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1107722

Other (OTH)

AF:

0.00

AC:

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 11, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.908T>C (p.I303T) alteration is located in exon 9 (coding exon 9) of the CDK14 gene. This alteration results from a T to C substitution at nucleotide position 908, causing the isoleucine (I) at amino acid position 303 to be replaced by a threonine (T). 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

0.99

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.;.;.

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Uncertain

0.099

MetaRNN

Pathogenic

0.89

D;D;D;D

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

1.9

L;.;.;.

PhyloP100

7.5

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-4.6

D;D;D;D

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

0.99

D;D;.;D

Vest4

0.95

MutPred

0.71

Loss of stability (P = 0.0626);.;.;.;

MVP

0.75

MPC

1.2

ClinPred

1.0

GERP RS

5.4

Varity_R

0.81

gMVP

0.90

Mutation Taster

=11/89

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over