rs992747412

Variant names:

• chr9-87967590-G-A
• rs992747412
• NM_001039803.3:c.913C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-87967590-G-A
• chr9-87967590-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001039803.3(CDK20):​c.913C>T​(p.Arg305Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,535,130 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. R305G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: CDK20 NM_001039803.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.39
• Publications: 0 publications found

Genes affected

CDK20 (HGNC:21420): (cyclin dependent kinase 20) The protein encoded by this gene contains a kinase domain most closely related to the cyclin-dependent protein kinases. The encoded kinase may activate cyclin-dependent kinase 2 and is involved in cell growth. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Dec 2009]

CDK20 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000303948 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36699438).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039803.3. 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
	CDK20	NM_001039803.3	MANE Select	c.913C>T	p.Arg305Cys	missense	Exon 8 of 8	NP_001034892.1	Q8IZL9-1
	CDK20	NM_178432.4		c.889C>T	p.Arg297Cys	missense	Exon 7 of 7	NP_848519.1	Q8IZL9-4
	CDK20	NM_012119.5		c.850C>T	p.Arg284Cys	missense	Exon 7 of 7	NP_036251.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK20	ENST00000325303.9	TSL:1 MANE Select	c.913C>T	p.Arg305Cys	missense	Exon 8 of 8	ENSP00000322343.8	Q8IZL9-1
	CDK20	ENST00000375883.7	TSL:1	c.850C>T	p.Arg284Cys	missense	Exon 7 of 7	ENSP00000365043.3	Q8IZL9-5
	CDK20	ENST00000605159.5	TSL:1	c.822C>T	p.Ser274Ser	synonymous	Exon 7 of 7	ENSP00000474485.1	Q8IZL9-3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD2 exomes AF: 0.0000277 AC: 4 AN: 144216 AF XY: 0.0000133

Gnomad AFR exome AF: 0.000231

Gnomad AMR exome AF: 0.0000428

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000940 AC: 13 AN: 1382900 Hom.: 0 Cov.: 31 AF XY: 0.00000736 AC XY: 5 AN XY: 679692

African (AFR) AF: 0.0000961 AC: 3 AN: 31214

American (AMR) AF: 0.0000582 AC: 2 AN: 34366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23964

East Asian (EAS) AF: 0.0000281 AC: 1 AN: 35528

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5596

European-Non Finnish (NFE) AF: 0.00000468 AC: 5 AN: 1069374

Other (OTH) AF: 0.0000175 AC: 1 AN: 57282

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74364

African (AFR) AF: 0.0000965 AC: 4 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	0.0020	D
PhyloP100		3.4
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.40		Loss of solvent accessibility (P = 0.0561)
MVP		0.54
MPC		0.25
ClinPred		0.92	D
GERP RS		4.7
Varity_R		0.35
gMVP		0.47
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs992747412; hg19: chr9-90582505; COSMIC: COSV100308152; COSMIC: COSV100308152;