6-110621247-C-A

Position:

• chr6-110621247-C-A

Variant summary

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

The NM_015076.5(CDK19):​c.1234G>T​(p.Ala412Ser) variant causes a missense 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. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK19 NM_015076.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.514

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.1234G>T	p.Ala412Ser	missense_variant	12/13	ENST00000368911.8	NP_055891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK19	ENST00000368911.8	c.1234G>T	p.Ala412Ser	missense_variant	12/13	1	NM_015076.5	ENSP00000357907.3
CDK19	ENST00000323817.7	c.1054G>T	p.Ala352Ser	missense_variant	13/14	1		ENSP00000317665.3
CDK19	ENST00000413605.6	c.922G>T	p.Ala308Ser	missense_variant	11/12	1		ENSP00000410604.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 87 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, Cologne University

May 13, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.0073	T;T;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	.;L;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.19	.;N;N
REVEL	Benign	0.024
Sift	Benign	0.27	.;T;T
Sift4G	Benign	0.85	T;T;T
Polyphen		0.037	.;B;.
Vest4		0.20
MutPred		0.33		.;Gain of glycosylation at A412 (P = 3e-04);.;
MVP		0.10
MPC		0.44
ClinPred		0.22	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.034
gMVP		0.065

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.68		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.68		Position offset: 6

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: chr6-110942450;