chr9-128333528-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_016035.5(COQ4):c.681C>T(p.Arg227=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000456 in 1,602,110 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 1 hom. )
Consequence
COQ4
NM_016035.5 synonymous
NM_016035.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.811
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 Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 9-128333528-C-T is Benign according to our data. Variant chr9-128333528-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 476187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.811 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ4 | NM_016035.5 | c.681C>T | p.Arg227= | synonymous_variant | 7/7 | ENST00000300452.8 | |
COQ4 | NM_001305942.2 | c.*57C>T | 3_prime_UTR_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ4 | ENST00000300452.8 | c.681C>T | p.Arg227= | synonymous_variant | 7/7 | 1 | NM_016035.5 | P1 | |
COQ4 | ENST00000461102.1 | n.2587C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152116Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000141 AC: 34AN: 241214Hom.: 0 AF XY: 0.0000763 AC XY: 10AN XY: 131018
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GnomAD4 exome AF: 0.0000441 AC: 64AN: 1449876Hom.: 1 Cov.: 30 AF XY: 0.0000416 AC XY: 30AN XY: 721038
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74424
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 02, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 30, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at