chr14-73950161-A-G
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The ENST00000554341.6(COQ6):c.69A>G(p.Pro23=) variant causes a synonymous, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,585,412 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0016 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
COQ6
ENST00000554341.6 synonymous, NMD_transcript
ENST00000554341.6 synonymous, NMD_transcript
Scores
1
13
Clinical Significance
Conservation
PhyloP100: 0.189
Genes affected
COQ6 (HGNC:20233): (coenzyme Q6, monooxygenase) The protein encoded by this gene belongs to the ubiH/COQ6 family. It is an evolutionarily conserved monooxygenase required for the biosynthesis of coenzyme Q10 (or ubiquinone), which is an essential component of the mitochondrial electron transport chain, and one of the most potent lipophilic antioxidants implicated in the protection of cell damage by reactive oxygen species. Knockdown of this gene in mouse and zebrafish results in decreased growth due to increased apoptosis. Mutations in this gene are associated with autosomal recessive coenzyme Q10 deficiency-6 (COQ10D6), which manifests as nephrotic syndrome with sensorineural deafness. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.003535539).
BP6
?
Variant 14-73950161-A-G is Benign according to our data. Variant chr14-73950161-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1187588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.189 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00161 (246/152346) while in subpopulation AFR AF= 0.00575 (239/41578). AF 95% confidence interval is 0.00515. There are 2 homozygotes in gnomad4. There are 136 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ6 | NM_182480.3 | c.69A>G | p.Pro23= | synonymous_variant | 1/12 | ||
COQ6 | XM_047431424.1 | c.69A>G | p.Pro23= | synonymous_variant | 1/11 | ||
COQ6 | XM_011536809.4 | c.-23A>G | 5_prime_UTR_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ6 | ENST00000554341.6 | c.69A>G | p.Pro23= | synonymous_variant, NMD_transcript_variant | 1/11 | 1 | |||
FAM161B | ENST00000651776.1 | c.55T>C | p.Trp19Arg | missense_variant | 1/9 | ||||
COQ6 | ENST00000394026.8 | c.69A>G | p.Pro23= | synonymous_variant | 1/12 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00156 AC: 237AN: 152228Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000425 AC: 86AN: 202438Hom.: 0 AF XY: 0.000241 AC XY: 27AN XY: 112158
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GnomAD4 exome AF: 0.000159 AC: 228AN: 1433066Hom.: 0 Cov.: 32 AF XY: 0.000112 AC XY: 80AN XY: 712474
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GnomAD4 genome ? AF: 0.00161 AC: 246AN: 152346Hom.: 2 Cov.: 33 AF XY: 0.00183 AC XY: 136AN XY: 74494
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
COQ6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 11, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Vest4
MutPred
Gain of methylation at W19 (P = 0.0062);
MVP
MPC
ClinPred
T
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Splicing
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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