rs886040973
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PS1PM1PP3PP5
The NM_016035.5(COQ4):c.197_198delinsAA(p.Arg66Gln) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin Lovd. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R66G) has been classified as Uncertain significance.
Frequency
Consequence
NM_016035.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ4 | NM_016035.5 | c.197_198delinsAA | p.Arg66Gln | missense_variant | 2/7 | ENST00000300452.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ4 | ENST00000300452.8 | c.197_198delinsAA | p.Arg66Gln | missense_variant | 2/7 | 1 | NM_016035.5 | P1 | |
COQ4 | ENST00000372875.3 | c.197_198delinsAA | p.Arg66Gln | missense_variant | 2/4 | 2 | |||
COQ4 | ENST00000608951.5 | c.197_198delinsAA | p.Arg66Gln | missense_variant | 2/3 | 2 | |||
COQ4 | ENST00000609948.1 | c.197_198delinsAA | p.Arg66Gln | missense_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 27, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 2022 | This variant has been observed in individual(s) with coenzyme Q10 deficiency (PMID: 26185144). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.1%). This variant, c.197_198delinsAA, is a complex sequence change that results in the change of 1 amino acid(s) in the COQ4 protein (p.Arg66Gln). ClinVar contains an entry for this variant (Variation ID: 267346). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 31, 2022 | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26185144) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at