chr17-39531119-A-G

Variant names:

• chr17-39531119-A-G
• rs587778178
• NM_016507.4:c.4276A>G

Variant summary

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

The NM_016507.4(CDK12):​c.4276A>G​(p.Ser1426Gly) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK12 NM_016507.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 4.78
• Publications: 1 publications found

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]

CDK12 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

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 (MetaRNN=0.11809811).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016507.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK12	NM_016507.4	MANE Select	c.4276A>G	p.Ser1426Gly	missense	Exon 14 of 14	NP_057591.2	Q9NYV4-1
	CDK12	NM_015083.4		c.4249A>G	p.Ser1417Gly	missense	Exon 14 of 14	NP_055898.1	Q9NYV4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK12	ENST00000447079.6	TSL:1 MANE Select	c.4276A>G	p.Ser1426Gly	missense	Exon 14 of 14	ENSP00000398880.4	Q9NYV4-1
	CDK12	ENST00000430627.6	TSL:1	c.4249A>G	p.Ser1417Gly	missense	Exon 14 of 14	ENSP00000407720.2	Q9NYV4-2
	CDK12	ENST00000922307.1		c.4198A>G	p.Ser1400Gly	missense	Exon 13 of 13	ENSP00000592366.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.11
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.23		Loss of disorder (P = 0.1245)
MVP		0.45
MPC		0.21
ClinPred		0.42	T
GERP RS		5.5
Varity_R		0.20
gMVP		0.16

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

Other links and lift over

dbSNP: rs587778178; hg19: chr17-37687372;