rs398122982
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024876.4(COQ8B):c.1199_1200insA(p.His400GlnfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
COQ8B
NM_024876.4 frameshift
NM_024876.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.62
Genes affected
COQ8B (HGNC:19041): (coenzyme Q8B) This gene encodes a protein with two copies of a domain found in protein kinases. The encoded protein has a complete protein kinase catalytic domain, and a truncated domain that contains only the active and binding sites of the protein kinase domain, however, it is not known whether the protein has any kinase activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-40695998-A-AT is Pathogenic according to our data. Variant chr19-40695998-A-AT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 91850.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ8B | NM_024876.4 | c.1199_1200insA | p.His400GlnfsTer11 | frameshift_variant | 13/15 | ENST00000324464.8 | |
COQ8B | NM_001142555.3 | c.1076_1077insA | p.His359GlnfsTer11 | frameshift_variant | 12/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ8B | ENST00000324464.8 | c.1199_1200insA | p.His400GlnfsTer11 | frameshift_variant | 13/15 | 1 | NM_024876.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251484Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135918
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461880Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727240
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GnomAD4 genome ? Cov.: 31
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nephrotic syndrome, type 9 Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 02, 2013 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | COQ8B: PVS1:Strong, PM2, PM3 - |
Computational scores
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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