rs144938364
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_018451.5(CENPJ):c.2462C>T(p.Thr821Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000476 in 1,614,134 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_018451.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CENPJ | NM_018451.5 | c.2462C>T | p.Thr821Met | missense_variant | 7/17 | ENST00000381884.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CENPJ | ENST00000381884.9 | c.2462C>T | p.Thr821Met | missense_variant | 7/17 | 1 | NM_018451.5 | P1 | |
CENPJ | ENST00000616936.4 | c.2462C>T | p.Thr821Met | missense_variant, NMD_transcript_variant | 7/16 | 1 | |||
CENPJ | ENST00000545981.6 | c.2462C>T | p.Thr821Met | missense_variant, NMD_transcript_variant | 7/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000703 AC: 107AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00148 AC: 372AN: 251412Hom.: 1 AF XY: 0.00130 AC XY: 177AN XY: 135872
GnomAD4 exome AF: 0.000453 AC: 662AN: 1461872Hom.: 4 Cov.: 34 AF XY: 0.000452 AC XY: 329AN XY: 727234
GnomAD4 genome ? AF: 0.000696 AC: 106AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.000886 AC XY: 66AN XY: 74462
ClinVar
Submissions by phenotype
Microcephaly 6, primary, autosomal recessive Pathogenic:1Uncertain:3
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2010 | - - |
Uncertain significance, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 12, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 31, 2017 | - - |
Seckel syndrome 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
CENPJ-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 08, 2023 | 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). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 17, 2023 | - - |
Seckel syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | Aug 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at