chr12-120528961-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032314.4(COQ5):c.181G>A(p.Glu61Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
COQ5
NM_032314.4 missense
NM_032314.4 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 6.58
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ5 | NM_032314.4 | c.181G>A | p.Glu61Lys | missense_variant | 1/7 | ENST00000288532.11 | |
COQ5 | XM_006719639.3 | c.-153G>A | 5_prime_UTR_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ5 | ENST00000288532.11 | c.181G>A | p.Glu61Lys | missense_variant | 1/7 | 1 | NM_032314.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251408Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135894
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461890Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727246
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74336
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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 | Apr 25, 2022 | The c.181G>A (p.E61K) alteration is located in exon 1 (coding exon 1) of the COQ5 gene. This alteration results from a G to A substitution at nucleotide position 181, causing the glutamic acid (E) at amino acid position 61 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;N
REVEL
Benign
Sift
Benign
T;T;D
Sift4G
Benign
T;T;D
Polyphen
P;B;.
Vest4
MutPred
Gain of methylation at E61 (P = 0.0123);Gain of methylation at E61 (P = 0.0123);Gain of methylation at E61 (P = 0.0123);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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