NM_001375405.1:c.1105C>T

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.1105C>T​(p.Pro369Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00288 in 1,613,972 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 68 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 59 hom. )

Consequence

CEP120
NM_001375405.1 missense

Scores

4
14

Clinical Significance

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

Conservation

PhyloP100: 4.11

Publications

5 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

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=0.002133131).
BP6
Variant 5-123390074-G-A is Benign according to our data. Variant chr5-123390074-G-A is described in ClinVar as [Benign]. Clinvar id is 476160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEP120NM_001375405.1 linkc.1105C>T p.Pro369Ser missense_variant Exon 8 of 20 ENST00000306467.10 NP_001362334.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEP120ENST00000306467.10 linkc.1105C>T p.Pro369Ser missense_variant Exon 8 of 20 5 NM_001375405.1 ENSP00000303058.6 Q8N960-1

Frequencies

GnomAD3 genomes
AF:
0.0158
AC:
2400
AN:
152034
Hom.:
68
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0555
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00485
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00862
GnomAD2 exomes
AF:
0.00381
AC:
951
AN:
249474
AF XY:
0.00291
show subpopulations
Gnomad AFR exome
AF:
0.0549
Gnomad AMR exome
AF:
0.00252
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000618
Gnomad OTH exome
AF:
0.000990
GnomAD4 exome
AF:
0.00154
AC:
2252
AN:
1461820
Hom.:
59
Cov.:
31
AF XY:
0.00127
AC XY:
920
AN XY:
727212
show subpopulations
African (AFR)
AF:
0.0560
AC:
1874
AN:
33472
American (AMR)
AF:
0.00273
AC:
122
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39692
South Asian (SAS)
AF:
0.0000348
AC:
3
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
0.000867
AC:
5
AN:
5766
European-Non Finnish (NFE)
AF:
0.0000495
AC:
55
AN:
1111970
Other (OTH)
AF:
0.00320
AC:
193
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.473
Heterozygous variant carriers
0
113
225
338
450
563
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
62
124
186
248
310
<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:
0.0158
AC:
2403
AN:
152152
Hom.:
68
Cov.:
32
AF XY:
0.0157
AC XY:
1164
AN XY:
74376
show subpopulations
African (AFR)
AF:
0.0554
AC:
2299
AN:
41502
American (AMR)
AF:
0.00484
AC:
74
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5190
South Asian (SAS)
AF:
0.000415
AC:
2
AN:
4816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10586
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.000147
AC:
10
AN:
68000
Other (OTH)
AF:
0.00853
AC:
18
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.509
Heterozygous variant carriers
0
113
227
340
454
567
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
26
52
78
104
130
<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:
0.00359
Hom.:
18
Bravo
AF:
0.0180
ESP6500AA
AF:
0.0527
AC:
196
ESP6500EA
AF:
0.000122
AC:
1
ExAC
AF:
0.00456
AC:
551
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Aug 25, 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
0.095
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.045
T;T;.;T
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.75
.;T;T;T
MetaRNN
Benign
0.0021
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;L;.;.
PhyloP100
4.1
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-2.2
N;N;N;N
REVEL
Benign
0.053
Sift
Benign
0.046
D;D;D;D
Sift4G
Benign
0.22
T;T;T;T
Polyphen
0.54
P;P;.;.
Vest4
0.34
MVP
0.52
MPC
0.30
ClinPred
0.010
T
GERP RS
4.3
Varity_R
0.097
gMVP
0.42
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs61747983; hg19: chr5-122725768; API