rs757499322
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Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001375408.1(CEP120):c.-298C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,599,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
CEP120
NM_001375408.1 5_prime_UTR_premature_start_codon_gain
NM_001375408.1 5_prime_UTR_premature_start_codon_gain
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 2.81
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 Likely_pathogenic. Variant got 8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
BayesDel_addAF computational evidence supports a deleterious effect, 0.553
PP5
Variant 5-123412411-G-A is Pathogenic according to our data. Variant chr5-123412411-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 446142.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-123412411-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CEP120 | NM_001375405.1 | c.451C>T | p.Arg151* | stop_gained | 4/20 | ENST00000306467.10 | NP_001362334.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CEP120 | ENST00000306467.10 | c.451C>T | p.Arg151* | stop_gained | 4/20 | 5 | NM_001375405.1 | ENSP00000303058.6 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000424 AC: 1AN: 235656Hom.: 0 AF XY: 0.00000780 AC XY: 1AN XY: 128142
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GnomAD4 exome AF: 0.0000111 AC: 16AN: 1447554Hom.: 0 Cov.: 30 AF XY: 0.0000139 AC XY: 10AN XY: 719894
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74340
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Chuvash polycythemia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Dec 17, 2024 | - - |
Short-rib thoracic dysplasia 13 with or without polydactyly Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 06, 2017 | - - |
Computational scores
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Name
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -12
Find out detailed SpliceAI scores and Pangolin per-transcript scores at