chr17-39462930-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016507.4(CDK12):āc.859T>Cā(p.Ser287Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
CDK12
NM_016507.4 missense
NM_016507.4 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 3.70
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]
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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=0.20509657).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDK12 | NM_016507.4 | c.859T>C | p.Ser287Pro | missense_variant | 1/14 | ENST00000447079.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDK12 | ENST00000447079.6 | c.859T>C | p.Ser287Pro | missense_variant | 1/14 | 1 | NM_016507.4 | P4 | |
CDK12 | ENST00000430627.6 | c.859T>C | p.Ser287Pro | missense_variant | 1/14 | 1 | A1 | ||
CDK12 | ENST00000584632.5 | c.859T>C | p.Ser287Pro | missense_variant | 1/13 | 5 | |||
CDK12 | ENST00000559663.2 | c.859T>C | p.Ser287Pro | missense_variant, NMD_transcript_variant | 1/21 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251412Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135912
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727246
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 22, 2023 | The c.859T>C (p.S287P) alteration is located in exon 1 (coding exon 1) of the CDK12 gene. This alteration results from a T to C substitution at nucleotide position 859, causing the serine (S) at amino acid position 287 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;N
REVEL
Benign
Sift
Uncertain
.;D;D
Sift4G
Uncertain
T;D;D
Polyphen
1.0, 0.99
.;D;D
Vest4
0.16, 0.24
MutPred
Loss of phosphorylation at S287 (P = 0.0013);Loss of phosphorylation at S287 (P = 0.0013);Loss of phosphorylation at S287 (P = 0.0013);
MVP
MPC
0.42
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at