chr19-40692253-G-GCAC
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_024876.4(COQ8B):c.1416_1417insGTG(p.Val472dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
COQ8B
NM_024876.4 inframe_insertion
NM_024876.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.192
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_024876.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ8B | NM_024876.4 | c.1416_1417insGTG | p.Val472dup | inframe_insertion | 15/15 | ENST00000324464.8 | |
COQ8B | NM_001142555.3 | c.1293_1294insGTG | p.Val431dup | inframe_insertion | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ8B | ENST00000324464.8 | c.1416_1417insGTG | p.Val472dup | inframe_insertion | 15/15 | 1 | NM_024876.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460808Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726670
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74280
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2022 | 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. This variant has not been reported in the literature in individuals affected with COQ8B-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.1414_1416dup, results in the insertion of 1 amino acid(s) of the COQ8B protein (p.Val472dup), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at