6-110622825-G-A

Position:

• chr6-110622825-G-A

Variant summary

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

The NM_015076.5(CDK19):​c.1021C>T​(p.Pro341Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK19 NM_015076.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.54

Genes affected

CDK19 (HGNC:19338): (cyclin dependent kinase 19) This gene encodes a protein that is one of the components of the Mediator co-activator complex. The Mediator complex is a multi-protein complex required for transcriptional activation by DNA binding transcription factors of genes transcribed by RNA polymerase II. The protein encoded by this gene is similar to cyclin-dependent kinase 8 which can also be a component of the Mediator complex. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

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
CDK19	NM_015076.5	c.1021C>T	p.Pro341Ser	missense_variant	10/13	ENST00000368911.8	NP_055891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK19	ENST00000368911.8	c.1021C>T	p.Pro341Ser	missense_variant	10/13	1	NM_015076.5	ENSP00000357907.3
CDK19	ENST00000323817.7	c.841C>T	p.Pro281Ser	missense_variant	11/14	1		ENSP00000317665.3
CDK19	ENST00000413605.6	c.709C>T	p.Pro237Ser	missense_variant	9/12	1		ENSP00000410604.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

CDK19-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 16, 2024

The CDK19 c.1021C>T variant is predicted to result in the amino acid substitution p.Pro341Ser. To our knowledge, this variant has not been reported in the literature or in a large population database, 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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.093	T;T;.
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Pathogenic	3.4	.;M;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-6.5	.;D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.027	.;D;D
Sift4G	Uncertain	0.018	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.68
MutPred		0.43		.;Loss of glycosylation at T342 (P = 0.067);.;
MVP		0.33
MPC		2.6
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.53

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: chr6-110944028;