rs114280473

Positions:

chr5-123378398-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0072216988).

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 male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP120	NM_001375405.1 linkuse as main transcript	c.2134C>T	p.Leu712Phe	missense_variant	15/20	ENST00000306467.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP120	ENST00000306467.10 linkuse as main transcript	c.2134C>T	p.Leu712Phe	missense_variant	15/20	5	NM_001375405.1	P1	Q8N960-1

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

GnomAD3 exomes

AF:

0.00377

AC:

914

AN:

242590

Hom.:

AF XY:

0.00377

AC XY:

496

AN XY:

131458

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 SAS 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

Gnomad4 AFR exome

AF:

0.000599

Gnomad4 AMR exome

AF:

0.00149

Gnomad4 ASJ exome

AF:

0.0000793

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.0152

Gnomad4 NFE exome

AF:

0.00441

Gnomad4 OTH exome

AF:

0.00269

GnomAD4 genome

AF:

0.00396

AC:

584

AN:

147584

Hom.:

Cov.:

AF XY:

0.00455

AC XY:

326

AN XY:

71680

show subpopulations

Gnomad4 AFR

AF:

0.000855

Gnomad4 AMR

AF:

0.00313

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0186

Gnomad4 NFE

AF:

0.00473

Gnomad4 OTH

AF:

0.00390

Alfa

AF:

0.00379

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

Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	CEP120: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 28, 2020	This variant is associated with the following publications: (PMID: 30988386, 27208211, 27270415) -
Uncertain significance, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Joubert syndrome 31

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 09, 2018

- -

CEP120-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 14, 2021

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

T;T;.;T

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

.;T;T;T

MetaRNN

Benign

0.0072

T;T;T;T

MetaSVM

Benign

-0.34

MutationAssessor

Pathogenic

2.9

M;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.95

MVP

0.80

MPC

0.45

ClinPred

0.065

GERP RS

5.8

Varity_R

0.65

gMVP

0.44

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

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