chr13-24906628-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The ENST00000381884.9(CENPJ):c.1410G>A(p.Pro470=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,614,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000071 ( 0 hom. )
Consequence
CENPJ
ENST00000381884.9 synonymous
ENST00000381884.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0850
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 -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 13-24906628-C-T is Benign according to our data. Variant chr13-24906628-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 158192.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=3}.
BP7
Synonymous conserved (PhyloP=0.085 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000532 (81/152338) while in subpopulation AFR AF= 0.00178 (74/41582). AF 95% confidence interval is 0.00145. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CENPJ | NM_018451.5 | c.1410G>A | p.Pro470= | synonymous_variant | 7/17 | ENST00000381884.9 | NP_060921.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CENPJ | ENST00000381884.9 | c.1410G>A | p.Pro470= | synonymous_variant | 7/17 | 1 | NM_018451.5 | ENSP00000371308 | P1 | |
| CENPJ | ENST00000616936.4 | c.1410G>A | p.Pro470= | synonymous_variant, NMD_transcript_variant | 7/16 | 1 | ENSP00000477511 | |||
| CENPJ | ENST00000545981.6 | c.1410G>A | p.Pro470= | synonymous_variant, NMD_transcript_variant | 7/18 | 2 | ENSP00000441090 |
Frequencies
GnomAD3 genomes 0.000526 AC: 80AN: 152220Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000227 AC: 57AN: 251152Hom.: 0 AF XY: 0.000192 AC XY: 26AN XY: 135742
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GnomAD4 exome AF: 0.0000711 AC: 104AN: 1461864Hom.: 0 Cov.: 34 AF XY: 0.0000715 AC XY: 52AN XY: 727226
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GnomAD4 genome 0.000532 AC: 81AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.000604 AC XY: 45AN XY: 74492
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:3
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2024 | CENPJ: BP4, BP7 - |
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 27, 2023 | - - |
| Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 13, 2020 | - - |
Microcephaly 6, primary, autosomal recessive Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at