rs1554796655
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016035.5(COQ4):c.67dup(p.Ala23GlyfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
COQ4
NM_016035.5 frameshift
NM_016035.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.318
Genes affected
COQ4 (HGNC:19693): (coenzyme Q4) This gene encodes a component of the coenzyme Q biosynthesis pathway. Coenzyme Q, an essential component of the electron transport chain, shuttles electrons between complexes I or II to complex III of the mitochondrial transport chain. This protein appears to play a structural role in stabilizing a complex that contains most of the coenzyme Q biosynthesis enzymes. Mutations in this gene are associated with mitochondrial disorders linked to coenzyme Q deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 59 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 9-128322923-C-CG is Pathogenic according to our data. Variant chr9-128322923-C-CG is described in ClinVar as [Pathogenic]. Clinvar id is 476186.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ4 | NM_016035.5 | c.67dup | p.Ala23GlyfsTer8 | frameshift_variant | 1/7 | ENST00000300452.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ4 | ENST00000300452.8 | c.67dup | p.Ala23GlyfsTer8 | frameshift_variant | 1/7 | 1 | NM_016035.5 | P1 | |
COQ4 | ENST00000372875.3 | c.67dup | p.Ala23GlyfsTer8 | frameshift_variant | 1/4 | 2 | |||
COQ4 | ENST00000608951.5 | c.67dup | p.Ala23GlyfsTer8 | frameshift_variant | 1/3 | 2 | |||
COQ4 | ENST00000609948.1 | c.67dup | p.Ala23GlyfsTer8 | frameshift_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2018 | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in COQ4 are known to be pathogenic (PMID: 25658047, 26185144). This sequence change inserts 1 nucleotide in exon 1 of the COQ4 mRNA (c.67dupG), causing a frameshift at codon 23. This creates a premature translational stop signal (p.Ala23Glyfs*8) and is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at