NM_001258.4:c.460G>A

Variant names:

• chr17-76002392-G-A
• rs145748425
• NM_001258.4:c.460G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001258.4(CDK3):​c.460G>A​(p.Val154Met) variant causes a missense change. The variant allele was found at a frequency of 0.000314 in 1,612,476 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (1 hom.)
• Consequence: CDK3 NM_001258.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.84
• Publications: 2 publications found

Genes affected

CDK3 (HGNC:1772): (cyclin dependent kinase 3) This gene encodes a member of the cyclin-dependent protein kinase family. The protein promotes entry into S phase, in part by activating members of the E2F family of transcription factors. The protein also associates with cyclin C and phosphorylates the retinoblastoma 1 protein to promote exit from G0. [provided by RefSeq, Jul 2008]

TEN1-CDK3 (HGNC:44420): (TEN1-CDK3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring TEN1 telomerase capping complex subunit homolog (S. cerevisiae) and cyclin-dependent kinase 3 (CDK3) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023290426).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258.4. 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
	CDK3	NM_001258.4	MANE Select	c.460G>A	p.Val154Met	missense	Exon 5 of 8	NP_001249.1	Q00526
	TEN1-CDK3	NR_037709.1		n.2296G>A		non_coding_transcript_exon	Exon 7 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK3	ENST00000448471.3	TSL:5 MANE Select	c.460G>A	p.Val154Met	missense	Exon 5 of 8	ENSP00000400088.1	Q00526
	CDK3	ENST00000425876.6	TSL:1	c.460G>A	p.Val154Met	missense	Exon 4 of 7	ENSP00000410561.1	Q00526
	TEN1-CDK3	ENST00000649294.1		n.*601G>A		non_coding_transcript_exon	Exon 8 of 11	ENSP00000497034.1

Frequencies

GnomAD3 genomes AF: 0.000316 AC: 48 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000368 AC: 92 AN: 249920 AF XY: 0.000400

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00457

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000370

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000314 AC: 459 AN: 1460308 Hom.: 1 Cov.: 32 AF XY: 0.000310 AC XY: 225 AN XY: 726464

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.0000671 AC: 3 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 113 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51958

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000272 AC: 303 AN: 1111960

Other (OTH) AF: 0.000431 AC: 26 AN: 60376

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74410

African (AFR) AF: 0.0000482 AC: 2 AN: 41528

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 67994

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000567 Hom.: 0

Bravo AF: 0.000306

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000420 AC: 51

EpiCase AF: 0.000709

EpiControl AF: 0.000178

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	Uncertain	0.38
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.85	L
PhyloP100		6.8
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.014	D
Polyphen		0.97	D
Vest4		0.80
MVP		0.53
MPC		0.89
ClinPred		0.20	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.34
Mutation Taster		=84/16	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: rs145748425; hg19: chr17-73998473;