chr7-39951707-C-G

Position:

chr7-39951707-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000181839.10(CDK13):c.1066C>G(p.Pro356Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,471,084 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 14 hom. )

Consequence

CDK13
ENST00000181839.10 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.207

Variant links:

Genes affected

CDK13 (HGNC:1733): (cyclin dependent kinase 13) The protein encoded by this gene is a member of the cyclin-dependent serine/threonine protein kinase family. Members of this family are well known for their essential roles as master switches in cell cycle control. The exact function of this protein has not yet been determined, but it may play a role in mRNA processing and may be involved in regulation of hematopoiesis. Alternatively spliced transcript variants have been described.[provided by RefSeq, Dec 2009]

CDK13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006324768).

BP6

Variant 7-39951707-C-G is Benign according to our data. Variant chr7-39951707-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 446011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00252 (384/152132) while in subpopulation NFE AF= 0.00443 (301/67974). AF 95% confidence interval is 0.00402. There are 1 homozygotes in gnomad4. There are 175 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 384 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK13	NM_003718.5 linkuse as main transcript	c.1066C>G	p.Pro356Ala	missense_variant	1/14	ENST00000181839.10	NP_003709.3	Q14004-1A0A024RA85Q9BVE2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK13	ENST00000181839.10 linkuse as main transcript	c.1066C>G	p.Pro356Ala	missense_variant	1/14	1	NM_003718.5	ENSP00000181839.4		Q14004-1

Frequencies

GnomAD3 genomes

AF:

0.00253

AC:

384

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00443

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00246

AC:

249

AN:

101338

Hom.:

AF XY:

0.00268

AC XY:

155

AN XY:

57776

show subpopulations

Gnomad AFR exome

AF:

0.000297

Gnomad AMR exome

AF:

0.00134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000903

Gnomad FIN exome

AF:

0.00150

Gnomad NFE exome

AF:

0.00410

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00347

AC:

4574

AN:

1318952

Hom.:

Cov.:

AF XY:

0.00335

AC XY:

2175

AN XY:

648656

show subpopulations

Gnomad4 AFR exome

AF:

0.000556

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.0000526

Gnomad4 EAS exome

AF:

0.0000304

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00183

Gnomad4 NFE exome

AF:

0.00407

Gnomad4 OTH exome

AF:

0.00269

GnomAD4 genome

AF:

0.00252

AC:

384

AN:

152132

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00443

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00257

Hom.:

Bravo

AF:

0.00290

ESP6500AA

AF:

0.00129

AC:

ESP6500EA

AF:

0.00258

AC:

ExAC

AF:

0.00219

AC:

245

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 19, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	CDK13: BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -

CDK13-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.14

T;.;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.62

T;T;T

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.0063

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;.

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.6

N;N;.

REVEL

Benign

0.054

Sift

Benign

0.14

T;T;.

Sift4G

Benign

0.082

T;T;.

Polyphen

0.0010

B;B;.

Vest4

0.051

MVP

0.40

MPC

0.14

ClinPred

0.025

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.15

gMVP

0.090

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over