rs17537669

chr7-39951707-C-Gchr7-39951707-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003718.5(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 NM_003718.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.207

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High AC in GnomAd at 384 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK13	NM_003718.5	c.1066C>G	p.Pro356Ala	missense_variant	1/14	ENST00000181839.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK13	ENST00000181839.10	c.1066C>G	p.Pro356Ala	missense_variant	1/14	1	NM_003718.5	P3

Frequencies

GnomAD3 genomes AF: 0.00253 AC: 384 AN: 152014 Hom.: 1 Cov.: 32

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.: 1 AF XY: 0.00268 AC XY: 155 AN XY: 57776

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.: 14 Cov.: 33 AF XY: 0.00335 AC XY: 2175 AN XY: 648656

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.: 1 Cov.: 32 AF XY: 0.00235 AC XY: 175 AN XY: 74386

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.: 0

Bravo AF: 0.00290

ESP6500AA AF: 0.00129 AC: 4

ESP6500EA AF: 0.00258 AC: 17

ExAC AF: 0.00219 AC: 245

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	CDK13: BS1 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 19, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 24, 2024	- -

CDK13-related disorder Benign:1

Likely benign, criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	12
Dann	Benign	0.93
DEOGEN2	Benign	0.14	T;.;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.62	T;T;T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.0063	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;.
MutationTaster	Benign	0.98	N;N
PrimateAI	Uncertain	0.75	T
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	T
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

Other links and lift over

dbSNP: rs17537669; hg19: chr7-39991306;