9-128332171-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016035.5(COQ4):c.421C>T(p.Arg141*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000697 in 1,577,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_016035.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COQ4 | NM_016035.5 | c.421C>T | p.Arg141* | stop_gained | Exon 5 of 7 | ENST00000300452.8 | NP_057119.3 | |
COQ4 | XM_047423449.1 | c.*21C>T | 3_prime_UTR_variant | Exon 4 of 4 | XP_047279405.1 | |||
COQ4 | NM_001305942.2 | c.*3-1303C>T | intron_variant | Intron 3 of 3 | NP_001292871.2 | |||
COQ4 | XM_017014792.2 | c.*3-679C>T | intron_variant | Intron 3 of 3 | XP_016870281.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000514 AC: 1AN: 194450Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 104204
GnomAD4 exome AF: 0.00000701 AC: 10AN: 1425538Hom.: 0 Cov.: 31 AF XY: 0.00000850 AC XY: 6AN XY: 705992
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome Pathogenic:2Other:1
This sequence change creates a premature translational stop signal (p.Arg141*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with coenzyme Q10 deficiency (PMID: 25658047). ClinVar contains an entry for this variant (Variation ID: 189200). For these reasons, this variant has been classified as Pathogenic. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at