rs1554102026

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5

The NM_001375405.1(CEP120):ā€‹c.2177T>Gā€‹(p.Leu726Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,830 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L726P) has been classified as Pathogenic.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 30)

Consequence

CEP120
NM_001375405.1 missense

Scores

7
9
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.83
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr5-123378355-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 446146.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CEP120NM_001375405.1 linkuse as main transcriptc.2177T>G p.Leu726Arg missense_variant 15/20 ENST00000306467.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CEP120ENST00000306467.10 linkuse as main transcriptc.2177T>G p.Leu726Arg missense_variant 15/205 NM_001375405.1 P1Q8N960-1

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151830
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151830
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
1
AN XY:
74156
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;T;.;T
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.88
.;D;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.72
D;D;D;D
MetaSVM
Uncertain
-0.14
T
MutationAssessor
Pathogenic
2.9
M;M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-4.5
D;D;D;D
REVEL
Uncertain
0.48
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Uncertain
0.027
D;D;D;D
Polyphen
1.0
D;D;.;.
Vest4
0.94
MutPred
0.28
Gain of solvent accessibility (P = 0.0055);Gain of solvent accessibility (P = 0.0055);.;.;
MVP
0.85
MPC
0.51
ClinPred
1.0
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.80
gMVP
0.72

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.

Other links and lift over

dbSNP: rs1554102026; hg19: chr5-122714049; API