NM_003718.5:c.94C>G

Variant names:

• chr7-39950735-C-G
• rs371265072
• NM_003718.5:c.94C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_003718.5(CDK13):​c.94C>G​(p.Leu32Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L32L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDK13 NM_003718.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.625
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• congenital heart defects, dysmorphic facial features, and intellectual developmental disorder

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Illumina
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06807089).
• BP6: Variant 7-39950735-C-G is Benign according to our data. Variant chr7-39950735-C-G is described in ClinVar as [Benign]. Clinvar id is 3014707.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK13	NM_003718.5	c.94C>G	p.Leu32Val	missense_variant	Exon 1 of 14	ENST00000181839.10	NP_003709.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK13	ENST00000181839.10	c.94C>G	p.Leu32Val	missense_variant	Exon 1 of 14	1	NM_003718.5	ENSP00000181839.4
CDK13	ENST00000340829.10	c.94C>G	p.Leu32Val	missense_variant	Exon 1 of 14	1		ENSP00000340557.5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1319012 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 650464

African (AFR) AF: 0.00 AC: 0 AN: 26472

American (AMR) AF: 0.00 AC: 0 AN: 24358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23068

East Asian (EAS) AF: 0.00 AC: 0 AN: 28598

South Asian (SAS) AF: 0.00 AC: 0 AN: 72050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3920

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1051234

Other (OTH) AF: 0.00 AC: 0 AN: 54734

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74330

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.093	T;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.60	T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.068	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N;N
PhyloP100		0.63
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.029
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.36	T;T
Polyphen		0.0	B;B
Vest4		0.079
MutPred		0.11		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.20
MPC		1.7
ClinPred		0.35	T
GERP RS		1.6
PromoterAI		-0.054	Neutral
Varity_R		0.25
gMVP		0.13
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs371265072; hg19: chr7-39990334;