7-39950756-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_003718.5(CDK13):c.115C>T(p.Leu39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000869 in 1,476,982 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (2 hom.)
• Consequence: CDK13 NM_003718.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.411

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 7-39950756-C-T is Benign according to our data. Variant chr7-39950756-C-T is described in ClinVar as [Benign]. Clinvar id is 725119.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.411 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000526 (80/152164) while in subpopulation NFE AF= 0.000823 (56/68018). AF 95% confidence interval is 0.000651. There are 0 homozygotes in gnomad4. There are 36 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 80 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK13	NM_003718.5	c.115C>T	p.Leu39=	synonymous_variant	1/14	ENST00000181839.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK13	ENST00000181839.10	c.115C>T	p.Leu39=	synonymous_variant	1/14	1	NM_003718.5	P3
CDK13	ENST00000340829.10	c.115C>T	p.Leu39=	synonymous_variant	1/14	1		A1

Frequencies

GnomAD3 genomes AF: 0.000526 AC: 80 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000514 AC: 41 AN: 79734 Hom.: 1 AF XY: 0.000351 AC XY: 16 AN XY: 45620

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000820

Gnomad ASJ exome AF: 0.000156

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000909

Gnomad OTH exome AF: 0.000425

GnomAD4 exome AF: 0.000908 AC: 1203 AN: 1324818 Hom.: 2 Cov.: 33 AF XY: 0.000840 AC XY: 549 AN XY: 653298

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.00108

Gnomad4 ASJ exome AF: 0.000214

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000137

Gnomad4 FIN exome AF: 0.0000582

Gnomad4 NFE exome AF: 0.00107

Gnomad4 OTH exome AF: 0.000727

GnomAD4 genome AF: 0.000526 AC: 80 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.000484 AC XY: 36 AN XY: 74334

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.000823

Gnomad4 OTH AF: 0.000958

Alfa AF: 0.000418 Hom.: 1

Bravo AF: 0.000544

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 17, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	14
Dann	Benign	0.97

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: rs756090286; hg19: chr7-39990355;