X-47224501-C-G

Position:

• chrX-47224501-C-G

Variant summary

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

The NM_006201.5(CDK16):​c.319C>G​(p.Arg107Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: CDK16 NM_006201.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.499

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.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK16	NM_006201.5	c.319C>G	p.Arg107Gly	missense_variant	3/16	ENST00000357227.9	NP_006192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK16	ENST00000357227.9	c.319C>G	p.Arg107Gly	missense_variant	3/16	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: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.541C>G (p.R181G) alteration is located in exon 3 (coding exon 3) of the CDK16 gene. This alteration results from a C to G substitution at nucleotide position 541, causing the arginine (R) at amino acid position 181 to be replaced by a glycine (G). 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	0.58
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;T;T;T;.;.;T;T;.
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D;.;D;D;D;D;D;D;D
M_CAP	Pathogenic	0.58	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.7	.;M;.;.;.;.;.;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.0	D;D;D;D;.;D;D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0090	D;D;D;D;.;D;D;D;D
Sift4G	Uncertain	0.026	D;D;T;T;D;D;T;D;D
Polyphen		0.71	.;P;.;.;.;.;.;P;.
Vest4		0.16
MutPred		0.45		.;Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);.;Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);.;
MVP		0.88
MPC		0.64
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.59
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.48		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.48		Position offset: 0

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-47083900;