rs543820987

Variant names:

• chr1-226986491-G-A
• rs543820987
• NM_020247.5:c.1698G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_020247.5(COQ8A):​c.1698G>A​(p.Leu566Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,612,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: COQ8A NM_020247.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

Genes affected

COQ8A (HGNC:16812): (coenzyme Q8A) This gene encodes a mitochondrial protein similar to yeast ABC1, which functions in an electron-transferring membrane protein complex in the respiratory chain. It is not related to the family of ABC transporter proteins. Expression of this gene is induced by the tumor suppressor p53 and in response to DNA damage, and inhibiting its expression partially suppresses p53-induced apoptosis. Alternatively spliced transcript variants have been found; however, their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

COQ8A Gene-Disease associations (from GenCC):

• autosomal recessive ataxia due to ubiquinone deficiency

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• coenzyme Q10 deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina

ENSG00000288674 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 1-226986491-G-A is Benign according to our data. Variant chr1-226986491-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 446791.
• BP7: Synonymous conserved (PhyloP=1.23 with no splicing effect.

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.1698G>A	p.Leu566Leu	synonymous	Exon 15 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.1698G>A	p.Leu566Leu	synonymous	Exon 15 of 15	ENSP00000355739.3
	COQ8A	ENST00000366778.5	TSL:1	c.1542G>A	p.Leu514Leu	synonymous	Exon 15 of 15	ENSP00000355740.1
	ENSG00000288674	ENST00000366779.6	TSL:2	n.*6425G>A		non_coding_transcript_exon	Exon 32 of 32	ENSP00000355741.2

Frequencies

GnomAD3 genomes AF: 0.0000987 AC: 15 AN: 151964 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 250810 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460730 Hom.: 0 Cov.: 60 AF XY: 0.00000826 AC XY: 6 AN XY: 726696

African (AFR) AF: 0.000358 AC: 12 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111562

Other (OTH) AF: 0.0000166 AC: 1 AN: 60364

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152082 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8 AN XY: 74318

African (AFR) AF: 0.000362 AC: 15 AN: 41478

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000763 Hom.: 0

Bravo AF: 0.000106

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.5
DANN	Benign	0.83
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs543820987; hg19: chr1-227174192;