6-110610228-G-T

Variant names:

• chr6-110610228-G-T
• rs10624
• NM_015076.5:c.*4307C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015076.5(CDK19):​c.*4307C>A variant causes a 3 prime UTR change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK19 NM_015076.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 87

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015076.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK19	NM_015076.5	MANE Select	c.*4307C>A		3_prime_UTR	Exon 13 of 13	NP_055891.1
	CDK19	NM_001300960.2		c.*4307C>A		3_prime_UTR	Exon 12 of 12	NP_001287889.1
	CDK19	NM_001300963.2		c.*4307C>A		3_prime_UTR	Exon 14 of 14	NP_001287892.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK19	ENST00000368911.8	TSL:1 MANE Select	c.*4307C>A		3_prime_UTR	Exon 13 of 13	ENSP00000357907.3
	CDK19	ENST00000323817.7	TSL:1	c.*4307C>A		3_prime_UTR	Exon 14 of 14	ENSP00000317665.3
	CDK19	ENST00000413605.6	TSL:1	c.*4307C>A		3_prime_UTR	Exon 12 of 12	ENSP00000410604.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.90
PhyloP100		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10624; hg19: chr6-110931431;