5-123346640-C-T

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.2840G>A(p.Arg947His) variant causes a missense change. The variant allele was found at a frequency of 0.0363 in 1,613,692 control chromosomes in the GnomAD database, including 1,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R947C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.046 ( 216 hom., cov: 33)

Exomes 𝑓: 0.035 ( 1468 hom. )

Consequence

CEP120
NM_001375405.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.51

Publications

20 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=0.0030833483).

BP6

Variant 5-123346640-C-T is Benign according to our data. Variant chr5-123346640-C-T is described in ClinVar as [Benign]. Clinvar id is 1168235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.095 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP120	NM_001375405.1 link	c.2840G>A	p.Arg947His	missense_variant	Exon 20 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.2840G>A	p.Arg947His	missense_variant	Exon 20 of 20	5	NM_001375405.1	ENSP00000303058.6		Q8N960-1

Frequencies

GnomAD3 genomes

AF:

0.0456

AC:

6930

AN:

152070

Hom.:

215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0465

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0746

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.0913

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0551

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0310

Gnomad OTH

AF:

0.0417

GnomAD2 exomes

AF:

0.0533

AC:

13380

AN:

250998

AF XY:

0.0539

show subpopulations

Gnomad AFR exome

AF:

0.0462

Gnomad AMR exome

AF:

0.0822

Gnomad ASJ exome

AF:

0.0132

Gnomad EAS exome

AF:

0.0893

Gnomad FIN exome

AF:

0.0601

Gnomad NFE exome

AF:

0.0297

Gnomad OTH exome

AF:

0.0428

GnomAD4 exome

AF:

0.0353

AC:

51630

AN:

1461504

Hom.:

1468

Cov.:

AF XY:

0.0372

AC XY:

27075

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.0459

AC:

1535

AN:

33472

American (AMR)

AF:

0.0824

AC:

3679

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.0130

AC:

340

AN:

26128

East Asian (EAS)

AF:

0.0808

AC:

3207

AN:

39682

South Asian (SAS)

AF:

0.0994

AC:

8568

AN:

86192

European-Finnish (FIN)

AF:

0.0612

AC:

3268

AN:

53392

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0256

AC:

28454

AN:

1111856

Other (OTH)

AF:

0.0411

AC:

2481

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

2489

4978

7468

9957

12446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0456

AC:

6943

AN:

152188

Hom.:

216

Cov.:

AF XY:

0.0486

AC XY:

3619

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0465

AC:

1933

AN:

41526

American (AMR)

AF:

0.0744

AC:

1138

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3468

East Asian (EAS)

AF:

0.0916

AC:

473

AN:

5166

South Asian (SAS)

AF:

0.102

AC:

494

AN:

4820

European-Finnish (FIN)

AF:

0.0551

AC:

584

AN:

10594

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0310

AC:

2108

AN:

68010

Other (OTH)

AF:

0.0450

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

341

682

1022

1363

1704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0342

Hom.:

533

Bravo

AF:

0.0444

TwinsUK

AF:

0.0237

AC:

ALSPAC

AF:

0.0234

AC:

ESP6500AA

AF:

0.0515

AC:

227

ESP6500EA

AF:

0.0280

AC:

241

ExAC

AF:

0.0533

AC:

6468

Asia WGS

AF:

0.111

AC:

387

AN:

3478

EpiCase

AF:

0.0269

EpiControl

AF:

0.0243

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 03, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 32772081) -

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

0.32

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

T;T;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

.;D;D

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M;.

PhyloP100

6.5

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.29

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.24

MPC

0.47

ClinPred

0.023

GERP RS

5.4

Varity_R

0.47

gMVP

0.53

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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5-123346640-C-T

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