13-24892817-T-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_018451.5(CENPJ):āc.3042A>Gā(p.Glu1014Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,610,908 control chromosomes in the GnomAD database, including 236,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.48 ( 18933 hom., cov: 29)
Exomes š: 0.54 ( 217968 hom. )
Consequence
CENPJ
NM_018451.5 synonymous
NM_018451.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.210
Genes affected
CENPJ (HGNC:17272): (centromere protein J) This gene encodes a protein that belongs to the centromere protein family. During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway, and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein. Mutations in this gene are associated with primary autosomal recessive microcephaly, a disorder characterized by severely reduced brain size and cognitive disability. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 13-24892817-T-C is Benign according to our data. Variant chr13-24892817-T-C is described in ClinVar as [Benign]. Clinvar id is 158207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-24892817-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.21 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CENPJ | ENST00000381884.9 | c.3042A>G | p.Glu1014Glu | synonymous_variant | 10/17 | 1 | NM_018451.5 | ENSP00000371308.4 | ||
CENPJ | ENST00000418179.1 | c.285A>G | p.Glu95Glu | synonymous_variant | 3/4 | 1 | ENSP00000399334.1 | |||
CENPJ | ENST00000616936.4 | n.3042A>G | non_coding_transcript_exon_variant | 10/16 | 1 | ENSP00000477511.1 | ||||
CENPJ | ENST00000545981.6 | n.3042A>G | non_coding_transcript_exon_variant | 10/18 | 2 | ENSP00000441090.2 |
Frequencies
GnomAD3 genomes AF: 0.483 AC: 73107AN: 151358Hom.: 18914 Cov.: 29
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GnomAD3 exomes AF: 0.549 AC: 137988AN: 251456Hom.: 39117 AF XY: 0.544 AC XY: 73993AN XY: 135906
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GnomAD4 exome AF: 0.543 AC: 792195AN: 1459432Hom.: 217968 Cov.: 44 AF XY: 0.541 AC XY: 393000AN XY: 726172
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GnomAD4 genome AF: 0.483 AC: 73158AN: 151476Hom.: 18933 Cov.: 29 AF XY: 0.490 AC XY: 36199AN XY: 73950
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ClinVar
Significance: Benign
Submissions summary: Benign:14
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 28, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 20, 2017 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Seckel syndrome 4 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Microcephaly 6, primary, autosomal recessive Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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