Variant 6-110621263-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015076.5(CDK19):c.1218C>G(p.Asn406Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CDK19
NM_015076.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.624

Variant links:

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]

CDK19 links:

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ACMG classification

Classification made for transcript

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=0.21913409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK19	NM_015076.5 linkuse as main transcript	c.1218C>G	p.Asn406Lys	missense_variant	12/13	ENST00000368911.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK19	ENST00000368911.8 linkuse as main transcript	c.1218C>G	p.Asn406Lys	missense_variant	12/13	1	NM_015076.5	P1	Q9BWU1-1
CDK19	ENST00000323817.7 linkuse as main transcript	c.1038C>G	p.Asn346Lys	missense_variant	13/14	1			Q9BWU1-2
CDK19	ENST00000413605.6 linkuse as main transcript	c.906C>G	p.Asn302Lys	missense_variant	11/12	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726690

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 22, 2023

The c.1218C>G (p.N406K) alteration is located in coding exon 12 of the CDK19 gene. This alteration results from a C to G substitution at nucleotide position 1218, causing the asparagine (N) at amino acid position 406 to be replaced by a lysine (K). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

3.4

DANN

Benign

0.95

DEOGEN2

Benign

0.020

T;T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.21

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.65

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.79

REVEL

Benign

0.27

Sift4G

Uncertain

0.031

D;T;T

Polyphen

1.0

.;D;.

Vest4

0.40

MutPred

0.32

.;Gain of ubiquitination at N406 (P = 0.0121);.;

MVP

0.23

MPC

1.4

ClinPred

0.82

GERP RS

-9.3

Varity_R

0.29

gMVP

0.37

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over