chr9-128322875-GCC-G
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016035.5(COQ4):c.19_20del(p.Pro7CysfsTer23) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,252 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R6R) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Consequence
COQ4
NM_016035.5 frameshift
NM_016035.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.06
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 60 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 9-128322875-GCC-G is Pathogenic according to our data. Variant chr9-128322875-GCC-G is described in ClinVar as [Pathogenic]. Clinvar id is 1455564.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.19_20del | p.Pro7CysfsTer23 | frameshift_variant | 1/7 | ENST00000300452.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ4 | ENST00000300452.8 | c.19_20del | p.Pro7CysfsTer23 | frameshift_variant | 1/7 | 1 | NM_016035.5 | P1 | |
COQ4 | ENST00000372875.3 | c.19_20del | p.Pro7CysfsTer23 | frameshift_variant | 1/4 | 2 | |||
COQ4 | ENST00000608951.5 | c.19_20del | p.Pro7CysfsTer23 | frameshift_variant | 1/3 | 2 | |||
COQ4 | ENST00000609948.1 | c.19_20del | p.Pro7CysfsTer23 | frameshift_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 33
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74386
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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 | Nov 18, 2023 | This sequence change creates a premature translational stop signal (p.Pro7Cysfs*23) in the COQ4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COQ4 are known to be pathogenic (PMID: 25658047). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COQ4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1455564). For these reasons, this variant has been classified as Pathogenic. - |
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