rs548317868
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM1BP4_StrongBP6
The NM_020247.5(COQ8A):c.1049A>G(p.Lys350Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,596,440 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K350E) has been classified as Uncertain significance.
Frequency
Consequence
NM_020247.5 missense
Scores
Clinical Significance
Conservation
Publications
- autosomal recessive ataxia due to ubiquinone deficiencyInheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
- coenzyme Q10 deficiencyInheritance: AR Classification: DEFINITIVE Submitted by: Illumina
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ACMG classification
Our verdict: Likely_benign. The variant received -3 ACMG points.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_020247.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| COQ8A | NM_020247.5 | MANE Select | c.1049A>G | p.Lys350Arg | missense | Exon 8 of 15 | NP_064632.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| COQ8A | ENST00000366777.4 | TSL:1 MANE Select | c.1049A>G | p.Lys350Arg | missense | Exon 8 of 15 | ENSP00000355739.3 | ||
| COQ8A | ENST00000366778.5 | TSL:1 | c.893A>G | p.Lys298Arg | missense | Exon 8 of 15 | ENSP00000355740.1 | ||
| ENSG00000288674 | ENST00000366779.6 | TSL:2 | n.*5776A>G | non_coding_transcript_exon | Exon 25 of 32 | ENSP00000355741.2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152218Hom.: 0 Cov.: 34 show subpopulations
GnomAD2 exomes AF: 0.000349 AC: 76AN: 217652 AF XY: 0.000498 show subpopulations
GnomAD4 exome AF: 0.000165 AC: 238AN: 1444104Hom.: 1 Cov.: 34 AF XY: 0.000251 AC XY: 180AN XY: 717148 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152336Hom.: 0 Cov.: 34 AF XY: 0.000107 AC XY: 8AN XY: 74488 show subpopulations
Age Distribution
ClinVar
ClinVar submissions as Germline
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at