Genetic Variant CDK7:p.Asn33Lys (chr5-69235426-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001799.4(CDK7):c.99C>G(p.Asn33Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CDK7
NM_001799.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.526

Publications

36 publications found

Variant links:

Genes affected

CDK7 (HGNC:1778): (cyclin dependent kinase 7) The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This protein forms a trimeric complex with cyclin H and MAT1, which functions as a Cdk-activating kinase (CAK). It is an essential component of the transcription factor TFIIH, that is involved in transcription initiation and DNA repair. This protein is thought to serve as a direct link between the regulation of transcription and the cell cycle. [provided by RefSeq, Jul 2008]

CDK7 links:

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ACMG classification

Classification was made for transcript

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=0.113809675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK7	NM_001799.4 link	c.99C>G	p.Asn33Lys	missense_variant	Exon 2 of 12	ENST00000256443.8	NP_001790.1	P50613A0A0S2Z3F9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK7	ENST00000256443.8 link	c.99C>G	p.Asn33Lys	missense_variant	Exon 2 of 12	1	NM_001799.4	ENSP00000256443.3		P50613

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1447828

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721186

African (AFR)

AF:

0.00

AC:

AN:

33060

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26058

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.00

AC:

AN:

85842

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099510

Other (OTH)

AF:

0.00

AC:

AN:

59880

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

17135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0080

.;T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

0.53

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.15

.;.;N;N

REVEL

Benign

0.078

Sift

Benign

0.88

.;.;T;T

Sift4G

Benign

0.84

T;T;T;T

Polyphen

0.0

.;.;B;.

Vest4

0.45

MutPred

0.37

Gain of methylation at N33 (P = 0.0342);Gain of methylation at N33 (P = 0.0342);Gain of methylation at N33 (P = 0.0342);Gain of methylation at N33 (P = 0.0342);

MVP

0.62

MPC

0.75

ClinPred

0.38

GERP RS

4.0

PromoterAI

0.013

Neutral

(source)

Varity_R

0.22

gMVP

0.27

Mutation Taster

=77/23

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over