X-47225031-A-C

Position:

• chrX-47225031-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006201.5(CDK16):​c.563A>C​(p.Asp188Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000913 in 1,095,410 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000091 (0 hom. 4 hem.)
• Consequence: CDK16 NM_006201.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.23

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]

CDK16 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK16	NM_006201.5	c.563A>C	p.Asp188Ala	missense_variant	6/16	ENST00000357227.9	NP_006192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK16	ENST00000357227.9	c.563A>C	p.Asp188Ala	missense_variant	6/16	1	NM_006201.5	ENSP00000349762.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000913 AC: 10 AN: 1095410 Hom.: 0 Cov.: 30 AF XY: 0.0000111 AC XY: 4 AN XY: 361074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000119

Gnomad4 OTH exome AF: 0.00

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

Apr 07, 2022

The c.785A>C (p.D262A) alteration is located in exon 6 (coding exon 6) of the CDK16 gene. This alteration results from a A to C substitution at nucleotide position 785, causing the aspartic acid (D) at amino acid position 262 to be replaced by an alanine (A). 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	0.68
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	.;T;.;.;T;T;.
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T;.;T;D;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.53	D;D;D;D;D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.58	.;N;.;.;.;N;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.0	D;D;.;D;D;D;D
REVEL	Benign	0.27
Sift	Benign	0.23	T;T;.;T;D;T;T
Sift4G	Benign	0.23	T;T;T;T;D;T;T
Polyphen		0.15	.;B;.;.;.;B;.
Vest4		0.38
MutPred		0.55		.;Gain of MoRF binding (P = 0.0473);.;Gain of MoRF binding (P = 0.0473);Gain of MoRF binding (P = 0.0473);Gain of MoRF binding (P = 0.0473);.;
MVP		0.84
MPC		2.4
ClinPred		0.93	D
GERP RS		5.8
Varity_R		0.86
gMVP		0.96

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

LitVar

Other links and lift over

dbSNP: rs1264123488; hg19: chrX-47084430;