Genetic Variant CDC123:p.Ile234Thr (chr10-12238469-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006023.3(CDC123):c.701T>C(p.Ile234Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000139 in 1,607,628 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 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

CDC123
NM_006023.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.55

Publications

1 publications found

Variant links:

Genes affected

CDC123 (HGNC:16827): (cell division cycle 123) Predicted to be involved in eukaryotic translation initiation factor 2 complex assembly and positive regulation of translational initiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CDC123 links:

ENSG00000228302 (HGNC:):

ENSG00000228302 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20798913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006023.3. 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
	CDC123	NM_006023.3	MANE Select	c.701T>C	p.Ile234Thr	missense	Exon 10 of 13	NP_006014.2	O75794

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDC123	ENST00000281141.9	TSL:1 MANE Select	c.701T>C	p.Ile234Thr	missense	Exon 10 of 13	ENSP00000281141.4	O75794
CDC123	ENST00000932716.1		c.821T>C	p.Ile274Thr	missense	Exon 11 of 14	ENSP00000602775.1
CDC123	ENST00000932723.1		c.800T>C	p.Ile267Thr	missense	Exon 11 of 14	ENSP00000602782.1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000216

AC:

AN:

244876

AF XY:

0.000219

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000612

Gnomad ASJ exome

AF:

0.00221

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000161

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.000131

AC:

191

AN:

1455424

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

723754

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33058

American (AMR)

AF:

0.0000928

AC:

AN:

43088

Ashkenazi Jewish (ASJ)

AF:

0.00246

AC:

AN:

25998

East Asian (EAS)

AF:

0.00

AC:

AN:

39518

South Asian (SAS)

AF:

0.000249

AC:

AN:

84414

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000766

AC:

AN:

1110088

Other (OTH)

AF:

0.000249

AC:

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000217

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000323

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000414

Hom.:

Bravo

AF:

0.000196

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000231

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000357

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.81

M_CAP

Benign

0.0088

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.65

MutationAssessor

Benign

2.0

PhyloP100

6.5

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.29

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0080

Polyphen

0.23

Vest4

0.78

MVP

0.60

MPC

0.63

ClinPred

0.075

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.73

Mutation Taster

=61/39

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over