Genetic Variant CEP120:p.Leu712Phe (chr5-123378398-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001375405.1(CEP120):c.2134C>T(p.Leu712Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00408 in 1,570,510 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0041 ( 22 hom. )

Consequence

CEP120
NM_001375405.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1U:2B:4

Conservation

PhyloP100: 5.47

Publications

11 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=0.0072216988).

BP6

Variant 5-123378398-G-A is Benign according to our data. Variant chr5-123378398-G-A is described in ClinVar as Benign. ClinVar VariationId is 446145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00396 (584/147584) while in subpopulation NFE AF = 0.00473 (318/67268). AF 95% confidence interval is 0.0043. There are 1 homozygotes in GnomAd4. There are 326 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 22 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375405.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP120	NM_001375405.1	MANE Select	c.2134C>T	p.Leu712Phe	missense	Exon 15 of 20	NP_001362334.1
CEP120	NM_153223.4		c.2134C>T	p.Leu712Phe	missense	Exon 16 of 21	NP_694955.2
CEP120	NM_001166226.2		c.2056C>T	p.Leu686Phe	missense	Exon 15 of 20	NP_001159698.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP120	ENST00000306467.10	TSL:5 MANE Select	c.2134C>T	p.Leu712Phe	missense	Exon 15 of 20	ENSP00000303058.6
CEP120	ENST00000508138.5	TSL:1	n.*1706C>T		non_coding_transcript_exon	Exon 18 of 23	ENSP00000422234.1
CEP120	ENST00000513565.6	TSL:1	n.*1344C>T		non_coding_transcript_exon	Exon 15 of 21	ENSP00000422089.2

Frequencies

GnomAD3 genomes

AF:

0.00396

AC:

584

AN:

147486

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000857

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00313

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00473

Gnomad OTH

AF:

0.00394

GnomAD2 exomes

AF:

0.00377

AC:

914

AN:

242590

AF XY:

0.00377

show subpopulations

Gnomad AFR exome

AF:

0.00109

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0162

Gnomad NFE exome

AF:

0.00441

Gnomad OTH exome

AF:

0.00275

GnomAD4 exome

AF:

0.00410

AC:

5830

AN:

1422926

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

2853

AN XY:

708804

show subpopulations

African (AFR)

AF:

0.000599

AC:

AN:

31696

American (AMR)

AF:

0.00149

AC:

AN:

42874

Ashkenazi Jewish (ASJ)

AF:

0.0000793

AC:

AN:

25218

East Asian (EAS)

AF:

0.00

AC:

AN:

37924

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84474

European-Finnish (FIN)

AF:

0.0152

AC:

797

AN:

52354

Middle Eastern (MID)

AF:

0.000713

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.00441

AC:

4786

AN:

1084324

Other (OTH)

AF:

0.00269

AC:

157

AN:

58448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

245

490

736

981

1226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

170

340

510

680

850

<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:

0.00396

AC:

584

AN:

147584

Hom.:

Cov.:

AF XY:

0.00455

AC XY:

326

AN XY:

71680

show subpopulations

African (AFR)

AF:

0.000855

AC:

AN:

39778

American (AMR)

AF:

0.00313

AC:

AN:

14716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

4938

South Asian (SAS)

AF:

0.00

AC:

AN:

4624

European-Finnish (FIN)

AF:

0.0186

AC:

178

AN:

9582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00473

AC:

318

AN:

67268

Other (OTH)

AF:

0.00390

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00381

Hom.:

Bravo

AF:

0.00286

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00430

AC:

ExAC

AF:

0.00353

AC:

429

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Uncertain:2Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2Benign:2

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CEP120: BS1, BS2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

May 28, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30988386, 27208211, 27270415)

Joubert syndrome 31

Pathogenic:1

Feb 09, 2018

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

CEP120-related disorder

Benign:1

Jan 14, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Short-rib thoracic dysplasia 13 with or without polydactyly

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0072

MetaSVM

Benign

-0.34

MutationAssessor

Pathogenic

2.9

PhyloP100

5.5

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.95

MVP

0.80

MPC

0.45

ClinPred

0.065

GERP RS

5.8

Varity_R

0.65

gMVP

0.44

Mutation Taster

=81/19

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over