chr12-120522305-A-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_032314.4(COQ5):c.261T>G(p.Ser87Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,602 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
COQ5
NM_032314.4 missense
NM_032314.4 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 0.888
Genes affected
COQ5 (HGNC:28722): (coenzyme Q5, methyltransferase) Enables 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase activity. Involved in methylation and ubiquinone biosynthetic process. Located in mitochondrial matrix. Part of protein-containing complex. Colocalizes with mitochondrial inner membrane. Implicated in primary coenzyme Q10 deficiency 9. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.968
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ5 | NM_032314.4 | c.261T>G | p.Ser87Arg | missense_variant | 2/7 | ENST00000288532.11 | |
COQ5 | XM_006719639.3 | c.18T>G | p.Ser6Arg | missense_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ5 | ENST00000288532.11 | c.261T>G | p.Ser87Arg | missense_variant | 2/7 | 1 | NM_032314.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461560Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727108
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74252
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 21, 2021 | The c.261T>G (p.S87R) alteration is located in exon 2 (coding exon 2) of the COQ5 gene. This alteration results from a T to G substitution at nucleotide position 261, causing the serine (S) at amino acid position 87 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;.;.;.
Polyphen
D;D;.;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0087);Gain of MoRF binding (P = 0.0087);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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