17-39462164-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_016507.4(CDK12):​c.93C>T​(p.Asn31Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CDK12
NM_016507.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.69
Variant links:
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 Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP7
Synonymous conserved (PhyloP=1.69 with no splicing effect.
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDK12NM_016507.4 linkuse as main transcriptc.93C>T p.Asn31Asn synonymous_variant 1/14 ENST00000447079.6 NP_057591.2 Q9NYV4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDK12ENST00000447079.6 linkuse as main transcriptc.93C>T p.Asn31Asn synonymous_variant 1/141 NM_016507.4 ENSP00000398880.4 Q9NYV4-1
CDK12ENST00000430627.6 linkuse as main transcriptc.93C>T p.Asn31Asn synonymous_variant 1/141 ENSP00000407720.2 Q9NYV4-2
CDK12ENST00000584632.5 linkuse as main transcriptc.93C>T p.Asn31Asn synonymous_variant 1/135 ENSP00000464641.1 J3QSD7
CDK12ENST00000559663.2 linkuse as main transcriptn.93C>T non_coding_transcript_exon_variant 1/215 ENSP00000453329.2 H0YLT2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251462
Hom.:
0
AF XY:
0.0000441
AC XY:
6
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461802
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsNov 22, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
CADD
Benign
13
DANN
Benign
0.94
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.8

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs781546834; hg19: chr17-37618417; API