X-47223750-T-C

Position:

• chrX-47223750-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_006201.5(CDK16):​c.193T>C​(p.Ser65Pro) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: CDK16 NM_006201.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.733

Genes affected

CDK16 (HGNC:8749): (cyclin dependent kinase 16) The protein encoded by this gene belongs to the cdc2/cdkx subfamily of the ser/thr family of protein kinases. It may play a role in signal transduction cascades in terminally differentiated cells; in exocytosis; and in transport of secretory cargo from the endoplasmic reticulum. This gene is thought to escape X inactivation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity CDK16_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14758325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK16	NM_006201.5	c.193T>C	p.Ser65Pro	missense_variant	2/16	ENST00000357227.9	NP_006192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK16	ENST00000357227.9	c.193T>C	p.Ser65Pro	missense_variant	2/16	1	NM_006201.5	ENSP00000349762	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

CDK16-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 12, 2024

The CDK16 c.415T>C variant is predicted to result in the amino acid substitution p.Ser139Pro. To our knowledge, this variant has not been reported in the literature or in gnomAD, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	.;T;T;T;.;.;T;T;.
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.83	T;.;T;T;T;T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.48	.;N;.;.;.;.;.;N;.
MutationTaster	Benign	0.77	N;N;N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.040	N;N;N;N;.;N;N;N;N
REVEL	Benign	0.086
Sift	Benign	0.046	D;T;T;T;.;T;T;T;D
Sift4G	Benign	0.24	T;T;T;T;T;T;T;T;T
Polyphen		0.0	.;B;.;.;.;.;.;B;.
Vest4		0.18
MutPred		0.17		.;Loss of phosphorylation at S65 (P = 0.0302);Loss of phosphorylation at S65 (P = 0.0302);Loss of phosphorylation at S65 (P = 0.0302);.;Loss of phosphorylation at S65 (P = 0.0302);Loss of phosphorylation at S65 (P = 0.0302);Loss of phosphorylation at S65 (P = 0.0302);.;
MVP		0.71
MPC		0.75
ClinPred		0.19	T
GERP RS		2.3
Varity_R		0.18
gMVP		0.18

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: chrX-47083149;