rs200743857

chr1-226986746-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2 BP4_Strong BP6_Very_Strong BS1

The NM_020247.5(COQ8A):c.*9G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000217 in 1,611,170 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: COQ8A NM_020247.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00300

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-226986746-G-A is Benign according to our data. Variant chr1-226986746-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 377448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00131 (199/152374) while in subpopulation AFR AF= 0.00474 (197/41586). AF 95% confidence interval is 0.0042. There are 1 homozygotes in gnomad4. There are 93 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ8A	NM_020247.5	c.*9G>A		3_prime_UTR_variant	15/15	ENST00000366777.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ8A	ENST00000366777.4	c.*9G>A		3_prime_UTR_variant	15/15	1	NM_020247.5	P1

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 199 AN: 152256 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00475

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000407 AC: 99 AN: 243048 Hom.: 0 AF XY: 0.000264 AC XY: 35 AN XY: 132498

Gnomad AFR exome AF: 0.00562

Gnomad AMR exome AF: 0.000322

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000508

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000104 AC: 151 AN: 1458796 Hom.: 0 Cov.: 33 AF XY: 0.0000827 AC XY: 60 AN XY: 725722

Gnomad4 AFR exome AF: 0.00379

Gnomad4 AMR exome AF: 0.000292

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000196

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome AF: 0.00131 AC: 199 AN: 152374 Hom.: 1 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74514

Gnomad4 AFR AF: 0.00474

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000971 Hom.: 0

Bravo AF: 0.00149

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 12, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.3
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs200743857; hg19: chr1-227174447;