rs114280473
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0040 ( 1 hom., cov: 30)
Exomes 𝑓: 0.0041 ( 22 hom. )
Consequence
CEP120
NM_001375405.1 missense
NM_001375405.1 missense
Scores
7
5
5
Clinical Significance
Conservation
PhyloP100: 5.47
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0072216988).
BP6
?
Variant 5-123378398-G-A is Benign according to our data. Variant chr5-123378398-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 446145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-123378398-G-A is described in Lovd as [Likely_pathogenic].
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 | 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 | c.2134C>T | p.Leu712Phe | missense_variant | 15/20 | 5 | NM_001375405.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00396 AC: 584AN: 147486Hom.: 1 Cov.: 30
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00377 AC: 914AN: 242590Hom.: 1 AF XY: 0.00377 AC XY: 496AN XY: 131458
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GnomAD4 exome AF: 0.00410 AC: 5830AN: 1422926Hom.: 22 Cov.: 31 AF XY: 0.00403 AC XY: 2853AN XY: 708804
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GnomAD4 genome ? AF: 0.00396 AC: 584AN: 147584Hom.: 1 Cov.: 30 AF XY: 0.00455 AC XY: 326AN XY: 71680
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ESP6500AA
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Pathogenic:1Uncertain:2Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | CEP120: BS1, BS2 - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 28, 2020 | This variant is associated with the following publications: (PMID: 30988386, 27208211, 27270415) - |
Joubert syndrome 31 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 09, 2018 | - - |
CEP120-related disorder Benign:1
Likely benign, criteria provided, single submitter | 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 | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at