1-226986637-GC-AT

Variant names:

• chr1-226986637-GC-AT
• NM_020247.5:c.1844_1845delGCinsAT
• COQ8A p.Gly615Asp

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PS1 PP3

The NM_020247.5(COQ8A):​c.1844_1845delGCinsAT​(p.Gly615Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G615S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COQ8A NM_020247.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.99
• 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: Uncertain_significance. The variant received 5 ACMG points.

• PS1: Transcript NM_020247.5 (COQ8A) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ8A	NM_020247.5	MANE Select	c.1844_1845delGCinsAT	p.Gly615Asp	missense	N/A	NP_064632.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ8A	ENST00000366777.4	TSL:1 MANE Select	c.1844_1845delGCinsAT	p.Gly615Asp	missense	N/A	ENSP00000355739.3	Q8NI60-1
	COQ8A	ENST00000366778.5	TSL:1	c.1688_1689delGCinsAT	p.Gly563Asp	missense	N/A	ENSP00000355740.1	Q8NI60-3
	ENSG00000288674	ENST00000366779.6	TSL:2	n.*6571_*6572delGCinsAT		non_coding_transcript_exon	Exon 32 of 32	ENSP00000355741.2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-227174338;