17-76002046-G-C

Position:

chr17-76002046-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001258.4(CDK3):c.219G>C(p.Glu73Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,614,070 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

CDK3
NM_001258.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

Variant links:

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]

CDK3 links:

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]

TEN1-CDK3 links:

TEN1-CDK3 (HGNC:):

TEN1-CDK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK3	NM_001258.4 linkuse as main transcript	c.219G>C	p.Glu73Asp	missense_variant	4/8	ENST00000448471.3	NP_001249.1	Q00526
TEN1-CDK3	NR_037709.1 linkuse as main transcript	n.2055G>C		non_coding_transcript_exon_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDK3	ENST00000448471.3 linkuse as main transcript	c.219G>C	p.Glu73Asp	missense_variant	4/8	5	NM_001258.4	ENSP00000400088.1	Q00526
TEN1-CDK3	ENST00000649294.1 linkuse as main transcript	n.*360G>C		non_coding_transcript_exon_variant	7/11			ENSP00000497034.1
TEN1-CDK3	ENST00000649294.1 linkuse as main transcript	n.*360G>C		3_prime_UTR_variant	7/11			ENSP00000497034.1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000191

AC:

AN:

251430

Hom.:

AF XY:

0.000235

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000122

AC:

179

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000210

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000119

Hom.:

Bravo

AF:

0.000208

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2024

The c.219G>C (p.E73D) alteration is located in exon 4 (coding exon 3) of the CDK3 gene. This alteration results from a G to C substitution at nucleotide position 219, causing the glutamic acid (E) at amino acid position 73 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.091

T;T;T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

D;D;.;D

M_CAP

Benign

0.0076

MetaRNN

Benign

0.024

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.82

.;L;L;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.54

.;N;N;.

REVEL

Benign

0.052

Sift

Benign

0.53

.;T;T;.

Sift4G

Benign

0.52

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.31

MutPred

0.41

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;

MVP

0.18

MPC

0.36

ClinPred

0.00095

GERP RS

1.4

Varity_R

0.043

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over