Genetic Variant NM_001375405.1:c.451C>G (chr5-123412411-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001375405.1(CEP120):c.451C>G(p.Arg151Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,556 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CEP120
NM_001375405.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.81

Publications

3 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP120	NM_001375405.1 link	c.451C>G	p.Arg151Gly	missense_variant	Exon 4 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.451C>G	p.Arg151Gly	missense_variant	Exon 4 of 20	5	NM_001375405.1	ENSP00000303058.6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000849

AC:

AN:

235656

AF XY:

0.0000156

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1447556

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719894

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32460

American (AMR)

AF:

0.00

AC:

AN:

40862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25518

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39330

South Asian (SAS)

AF:

0.00

AC:

AN:

83094

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107618

Other (OTH)

AF:

0.0000167

AC:

AN:

59740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Uncertain

0.086

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

D;D;.;D;.

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.0

.;D;D;D;D

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.51

D;D;D;D;D

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.3

M;M;.;.;.

PhyloP100

2.8

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.9

D;D;D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0040

D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;.

Vest4

0.72

ClinPred

0.95

GERP RS

4.7

Varity_R

0.46

gMVP

0.58

Mutation Taster

=19/81

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over