X-47218663-AG-A

Position:

• chrX-47218663-AG-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_Strong BS2

The ENST00000457458.6(CDK16):​c.12+1delG variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,054,631 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000012 (0 hom. 5 hem.)
• Consequence: CDK16 ENST00000457458.6 splice_donor, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.74

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 Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.28561962 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8.5, offset of -1, new splice context is: cgaGTgagt. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK16	NM_006201.5	c.-448delG		upstream_gene_variant		ENST00000357227.9	NP_006192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK16	ENST00000357227.9	c.-448delG		upstream_gene_variant		1	NM_006201.5	ENSP00000349762.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000123 AC: 13 AN: 1054631 Hom.: 0 Cov.: 31 AF XY: 0.0000145 AC XY: 5 AN XY: 344661

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: 0.0000146

Gnomad4 OTH exome AF: 0.0000225

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

CDK16-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 21, 2023

The CDK16 c.12+1delG variant is predicted to result in a frameshift and premature protein termination (p.Ile5Serfs*6). This variant occurs in a the precoding region of the primary transcript for this gene (NM_006201.4:c.-447delG). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), 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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1937178226; hg19: chrX-47078062;