rs200061825
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_018451.5(CENPJ):c.600G>T(p.Gln200His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000682 in 1,613,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CENPJ | NM_018451.5 | c.600G>T | p.Gln200His | missense_variant | 4/17 | ENST00000381884.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CENPJ | ENST00000381884.9 | c.600G>T | p.Gln200His | missense_variant | 4/17 | 1 | NM_018451.5 | P1 | |
CENPJ | ENST00000616936.4 | c.600G>T | p.Gln200His | missense_variant, NMD_transcript_variant | 4/16 | 1 | |||
CENPJ | ENST00000545981.6 | c.600G>T | p.Gln200His | missense_variant, NMD_transcript_variant | 4/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000427 AC: 65AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251044Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135694
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461138Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 726882
GnomAD4 genome ? AF: 0.000427 AC: 65AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39AN XY: 74454
ClinVar
Submissions by phenotype
Microcephaly 6, primary, autosomal recessive Uncertain:2
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 11, 2013 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2022 | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 200 of the CENPJ protein (p.Gln200His). This variant is present in population databases (rs200061825, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CENPJ-related conditions. ClinVar contains an entry for this variant (Variation ID: 158216). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 27, 2017 | - - |
Microcephaly 6, primary, autosomal recessive;C3888212:Seckel syndrome 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 23, 2023 | The c.600G>T (p.Q200H) alteration is located in exon 4 (coding exon 3) of the CENPJ gene. This alteration results from a G to T substitution at nucleotide position 600, causing the glutamine (Q) at amino acid position 200 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Seckel syndrome 4 Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at