Genetic Variant CDK7:p.Asn35His (chr5-69235430-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001799.4(CDK7):c.103A>C(p.Asn35His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,603,324 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CDK7
NM_001799.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.773

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 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=0.188256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK7	NM_001799.4 link	c.103A>C	p.Asn35His	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.103A>C	p.Asn35His	missense_variant	Exon 2 of 12	1	NM_001799.4	ENSP00000256443.3		P50613

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450986

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722620

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Uncertain

0.97

DEOGEN2

Benign

0.034

.;T;T;T

Eigen

Benign

0.035

Eigen_PC

Benign

0.068

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-0.84

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.8

.;.;D;D

REVEL

Benign

0.090

Sift

Uncertain

0.019

.;.;D;D

Sift4G

Benign

0.091

T;T;D;D

Polyphen

0.74

.;.;P;.

Vest4

0.29

MutPred

0.58

Loss of MoRF binding (P = 0.1177);Loss of MoRF binding (P = 0.1177);Loss of MoRF binding (P = 0.1177);Loss of MoRF binding (P = 0.1177);

MVP

0.77

MPC

1.2

ClinPred

0.89

GERP RS

2.4

Varity_R

0.47

gMVP

0.25

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over