rs769526109

Variant names:

• chr7-39950688-G-A
• rs769526109
• NM_003718.5:c.47G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-39950688-G-A
• chr7-39950688-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003718.5(CDK13):​c.47G>A​(p.Ser16Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 1,277,098 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S16R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: CDK13 NM_003718.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086508185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK13	NM_003718.5	c.47G>A	p.Ser16Asn	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.47G>A	p.Ser16Asn	missense_variant	Exon 1 of 14	1	NM_003718.5	ENSP00000181839.4
CDK13	ENST00000340829.10	c.47G>A	p.Ser16Asn	missense_variant	Exon 1 of 14	1		ENSP00000340557.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000313 AC: 4 AN: 1277098 Hom.: 0 Cov.: 33 AF XY: 0.00000479 AC XY: 3 AN XY: 625826

African (AFR) AF: 0.00 AC: 0 AN: 25646

American (AMR) AF: 0.00 AC: 0 AN: 19792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20426

East Asian (EAS) AF: 0.00 AC: 0 AN: 28024

South Asian (SAS) AF: 0.0000308 AC: 2 AN: 65002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3750

European-Non Finnish (NFE) AF: 0.00000194 AC: 2 AN: 1028646

Other (OTH) AF: 0.00 AC: 0 AN: 52862

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.069	T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.56	T;T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;N
PhyloP100		1.9
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-0.080	N;N
REVEL	Benign	0.043
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.023	B;B
Vest4		0.12
MutPred		0.076		Loss of phosphorylation at S16 (P = 0.0145);Loss of phosphorylation at S16 (P = 0.0145);
MVP		0.20
MPC		1.6
ClinPred		0.55	D
GERP RS		2.8
PromoterAI		0.014	Neutral
Varity_R		0.29
gMVP		0.43
Mutation Taster		=98/2	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: rs769526109; hg19: chr7-39990287;