dbSNP rs767194171: CDK14:p.Phe129Tyr (chr7-90747697-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001287135.2(CDK14):c.386T>A(p.Phe129Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,444,966 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F129C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CDK14
NM_001287135.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.66

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK14	NM_001287135.2 link	c.386T>A	p.Phe129Tyr	missense_variant	Exon 4 of 15	ENST00000380050.8	NP_001274064.1	O94921-1
CDK14	NM_012395.3 link	c.332T>A	p.Phe111Tyr	missense_variant	Exon 3 of 14		NP_036527.1	O94921-2
CDK14	NM_001287136.1 link	c.248T>A	p.Phe83Tyr	missense_variant	Exon 3 of 14		NP_001274065.1	O94921-3
CDK14	NM_001287137.1 link	c.77+20885T>A		intron_variant	Intron 2 of 12		NP_001274066.1	O94921E7EUK8B4DK59

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK14	ENST00000380050.8 link	c.386T>A	p.Phe129Tyr	missense_variant	Exon 4 of 15	1	NM_001287135.2	ENSP00000369390.3		O94921-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000425

AC:

AN:

235094

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000917

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1444966

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718660

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32456

American (AMR)

AF:

0.00

AC:

AN:

40850

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25860

East Asian (EAS)

AF:

0.00

AC:

AN:

38634

South Asian (SAS)

AF:

0.00

AC:

AN:

82606

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1105788

Other (OTH)

AF:

0.00

AC:

AN:

59762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.10

T;T;T;T;T;T;.;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;.;.;D;D;D;D;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.46

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

0.55

.;.;.;.;N;.;.;.

PhyloP100

7.7

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-2.5

D;D;D;D;N;D;N;N

REVEL

Benign

0.25

Sift

Benign

0.031

D;D;D;D;T;D;D;D

Sift4G

Uncertain

0.039

D;D;D;D;T;D;T;T

Polyphen

0.11, 1.0

.;.;.;.;B;.;D;.

Vest4

0.65, 0.69, 0.69

MutPred

0.24

.;.;.;.;Gain of phosphorylation at F129 (P = 0.0073);.;.;.;

MVP

0.78

MPC

0.86

ClinPred

0.79

GERP RS

5.9

Varity_R

0.40

gMVP

0.57

Mutation Taster

=22/78

disease causing

(source)

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

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rs767194171

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over