X-47223288-A-G

Position:

• chrX-47223288-A-G

Variant summary

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

The NM_006201.5(CDK16):​c.-6-264A>G variant causes a intron 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: CDK16 NM_006201.5 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18671528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK16	NM_006201.5	c.-6-264A>G		intron_variant		ENST00000357227.9	NP_006192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK16	ENST00000357227.9	c.-6-264A>G		intron_variant		1	NM_006201.5	ENSP00000349762	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 33

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

Jan 24, 2024

The c.193A>G (p.S65G) alteration is located in exon 1 (coding exon 1) of the CDK16 gene. This alteration results from a A to G substitution at nucleotide position 193, causing the serine (S) at amino acid position 65 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
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.50
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.38	T
Vest4		0.20
MutPred		0.21		Loss of helix (P = 0.0068);
MVP		0.84
MPC		0.38
ClinPred		0.24	T
GERP RS		4.4
gMVP		0.072

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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-47082687;