chr13-24905568-T-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_018451.5(CENPJ):c.2470A>T(p.Thr824Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,614,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_018451.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CENPJ | NM_018451.5 | c.2470A>T | p.Thr824Ser | missense_variant | 7/17 | ENST00000381884.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CENPJ | ENST00000381884.9 | c.2470A>T | p.Thr824Ser | missense_variant | 7/17 | 1 | NM_018451.5 | P1 | |
CENPJ | ENST00000616936.4 | c.2470A>T | p.Thr824Ser | missense_variant, NMD_transcript_variant | 7/16 | 1 | |||
CENPJ | ENST00000545981.6 | c.2470A>T | p.Thr824Ser | missense_variant, NMD_transcript_variant | 7/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000230 AC: 35AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251434Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135888
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461884Hom.: 0 Cov.: 34 AF XY: 0.0000220 AC XY: 16AN XY: 727240
GnomAD4 genome ? AF: 0.000295 AC: 45AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28AN XY: 74492
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 158202). This variant has not been reported in the literature in individuals affected with CENPJ-related conditions. This variant is present in population databases (rs149885751, gnomAD 0.07%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 824 of the CENPJ protein (p.Thr824Ser). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 02, 2016 | - - |
Microcephaly 6, primary, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 31, 2012 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at