chr17-39530702-T-C

Position:

• chr17-39530702-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016507.4(CDK12):​c.3859T>C​(p.Ser1287Pro) variant causes a missense 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: CDK12 NM_016507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74

Genes affected

CDK12 (HGNC:24224): (cyclin dependent kinase 12) Enables RNA polymerase II CTD heptapeptide repeat kinase activity and cyclin binding activity. Involved in phosphorylation of RNA polymerase II C-terminal domain; protein autophosphorylation; and regulation of MAP kinase activity. Located in nuclear speck. Part of cyclin K-CDK12 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2765833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK12	NM_016507.4	c.3859T>C	p.Ser1287Pro	missense_variant	14/14	ENST00000447079.6	NP_057591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK12	ENST00000447079.6	c.3859T>C	p.Ser1287Pro	missense_variant	14/14	1	NM_016507.4	ENSP00000398880	P4
CDK12	ENST00000430627.6	c.3832T>C	p.Ser1278Pro	missense_variant	14/14	1		ENSP00000407720	A1
CDK12	ENST00000584336.1	n.821T>C		non_coding_transcript_exon_variant	1/1
CDK12	ENST00000559663.2	c.3760+4386T>C		intron_variant, NMD_transcript_variant		5		ENSP00000453329

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.8	.;L
MutationTaster	Benign	0.70	D;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.3	N;N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0010	D;D
Sift4G	Benign	0.29	T;T
Polyphen		0.99	D;D
Vest4		0.56
MutPred		0.067		.;Loss of phosphorylation at S1287 (P = 0.021);
MVP		0.64
MPC		0.79
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.29
gMVP		0.20

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

LitVar

Other links and lift over

dbSNP: rs587778179; hg19: chr17-37686955;