7-39951119-G-C

Variant names:

• chr7-39951119-G-C
• rs1554317112
• NM_003718.5:c.478G>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.478G>C​(p.Gly160Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,092,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G160V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: CDK13 NM_003718.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 2.39
• 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: G2P, Labcorp Genetics (formerly Invitae), 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=0.15421104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003718.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK13	NM_003718.5	MANE Select	c.478G>C	p.Gly160Arg	missense	Exon 1 of 14	NP_003709.3
	CDK13	NM_031267.3		c.478G>C	p.Gly160Arg	missense	Exon 1 of 14	NP_112557.2	Q9BVE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK13	ENST00000181839.10	TSL:1 MANE Select	c.478G>C	p.Gly160Arg	missense	Exon 1 of 14	ENSP00000181839.4	Q14004-1
	CDK13	ENST00000340829.10	TSL:1	c.478G>C	p.Gly160Arg	missense	Exon 1 of 14	ENSP00000340557.5	Q14004-2
	CDK13	ENST00000966764.1		c.478G>C	p.Gly160Arg	missense	Exon 1 of 14	ENSP00000636823.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1092704 Hom.: 0 Cov.: 33 AF XY: 0.00000193 AC XY: 1 AN XY: 517130

African (AFR) AF: 0.00 AC: 0 AN: 22978

American (AMR) AF: 0.000119 AC: 1 AN: 8424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14538

East Asian (EAS) AF: 0.00 AC: 0 AN: 26530

South Asian (SAS) AF: 0.00 AC: 0 AN: 22254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 927708

Other (OTH) AF: 0.00 AC: 0 AN: 44298

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.4
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.031
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.042	D
Polyphen		0.053	B
Vest4		0.13
MutPred		0.22		Gain of helix (P = 0.0325)
MVP		0.26
MPC		2.0
ClinPred		0.42	T
GERP RS		2.9
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.25
gMVP		0.20
Mutation Taster		=72/28	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: rs1554317112; hg19: chr7-39990718;