5-123383042-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001375405.1(CEP120):c.1804C>G(p.Leu602Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,557,710 control chromosomes in the GnomAD database, including 138,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L602L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.40 ( 12285 hom., cov: 33)

Exomes 𝑓: 0.42 ( 126162 hom. )

Consequence

CEP120
NM_001375405.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.83

Publications

41 publications found

Variant links:

Genes affected

CEP120 (HGNC:26690): (centrosomal protein 120) This gene encodes a protein that functions in the microtubule-dependent coupling of the nucleus and the centrosome. A similar protein in mouse plays a role in both interkinetic nuclear migration, which is a characteristic pattern of nuclear movement in neural progenitors, and in neural progenitor self-renewal. Mutations in this gene are predicted to result in neurogenic defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

CEP120 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
Joubert syndrome 31
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
short-rib thoracic dysplasia 13 with or without polydactyly
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Jeune syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with ocular defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP120 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030404925).

BP6

Variant 5-123383042-G-C is Benign according to our data. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123383042-G-C is described in CliVar as Benign. Clinvar id is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP120	NM_001375405.1 link	c.1804C>G	p.Leu602Val	missense_variant	Exon 12 of 20	ENST00000306467.10	NP_001362334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP120	ENST00000306467.10 link	c.1804C>G	p.Leu602Val	missense_variant	Exon 12 of 20	5	NM_001375405.1	ENSP00000303058.6		Q8N960-1

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60719

AN:

151912

Hom.:

12282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.363

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.424

GnomAD2 exomes

AF:

0.421

AC:

103140

AN:

245190

AF XY:

0.425

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.390

Gnomad ASJ exome

AF:

0.347

Gnomad EAS exome

AF:

0.478

Gnomad FIN exome

AF:

0.441

Gnomad NFE exome

AF:

0.428

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.421

AC:

591916

AN:

1405680

Hom.:

126162

Cov.:

AF XY:

0.423

AC XY:

297017

AN XY:

701742

show subpopulations

African (AFR)

AF:

0.317

AC:

10270

AN:

32408

American (AMR)

AF:

0.394

AC:

17252

AN:

43738

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

8871

AN:

25630

East Asian (EAS)

AF:

0.470

AC:

18486

AN:

39316

South Asian (SAS)

AF:

0.461

AC:

38642

AN:

83884

European-Finnish (FIN)

AF:

0.442

AC:

23484

AN:

53114

Middle Eastern (MID)

AF:

0.471

AC:

2648

AN:

5626

European-Non Finnish (NFE)

AF:

0.421

AC:

448097

AN:

1063580

Other (OTH)

AF:

0.414

AC:

24166

AN:

58384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

14449

28898

43346

57795

72244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13468

26936

40404

53872

67340

<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:

0.400

AC:

60747

AN:

152030

Hom.:

12285

Cov.:

AF XY:

0.401

AC XY:

29796

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.321

AC:

13310

AN:

41462

American (AMR)

AF:

0.410

AC:

6260

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.363

AC:

1261

AN:

3470

East Asian (EAS)

AF:

0.478

AC:

2474

AN:

5174

South Asian (SAS)

AF:

0.467

AC:

2252

AN:

4824

European-Finnish (FIN)

AF:

0.451

AC:

4760

AN:

10554

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.428

AC:

29107

AN:

67956

Other (OTH)

AF:

0.425

AC:

900

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1888

3776

5665

7553

9441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.377

Hom.:

3299

Bravo

AF:

0.394

TwinsUK

AF:

0.416

AC:

1542

ALSPAC

AF:

0.430

AC:

1656

ESP6500AA

AF:

0.322

AC:

1415

ESP6500EA

AF:

0.427

AC:

3666

ExAC

AF:

0.420

AC:

50953

Asia WGS

AF:

0.470

AC:

1633

AN:

3476

EpiCase

AF:

0.431

EpiControl

AF:

0.427

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Short-rib thoracic dysplasia 13 with or without polydactyly

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T;.;T

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

.;D;D;D

MetaRNN

Benign

0.0030

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.8

M;M;.;.

PhyloP100

2.8

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.1

N;N;N;N

REVEL

Benign

0.20

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.33

MPC

0.43

ClinPred

0.023

GERP RS

1.9

Varity_R

0.34

gMVP

0.52

Mutation Taster

=95/5

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over