rs150541057

chr1-226961463-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020247.5(COQ8A):c.78C>T(p.His26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,613,896 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: COQ8A NM_020247.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.736

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 1-226961463-C-T is Benign according to our data. Variant chr1-226961463-C-T is described in ClinVar as [Benign]. Clinvar id is 136296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-226961463-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.736 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00192 (293/152378) while in subpopulation AFR AF= 0.00656 (273/41594). AF 95% confidence interval is 0.00592. There are 3 homozygotes in gnomad4. There are 148 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ8A	NM_020247.5	c.78C>T	p.His26=	synonymous_variant	2/15	ENST00000366777.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ8A	ENST00000366777.4	c.78C>T	p.His26=	synonymous_variant	2/15	1	NM_020247.5	P1
COQ8A	ENST00000366778.5	c.-34-45C>T		intron_variant		1
COQ8A	ENST00000489044.1	n.289C>T		non_coding_transcript_exon_variant	2/5	3
COQ8A	ENST00000478406.5	n.107-15986C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 294 AN: 152260 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00658

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

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: 0.0000588

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.000478 AC: 120 AN: 251124 Hom.: 0 AF XY: 0.000324 AC XY: 44 AN XY: 135838

Gnomad AFR exome AF: 0.00641

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000168 AC: 246 AN: 1461518 Hom.: 0 Cov.: 31 AF XY: 0.000144 AC XY: 105 AN XY: 727074

Gnomad4 AFR exome AF: 0.00600

Gnomad4 AMR exome AF: 0.000402

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.00000629

Gnomad4 OTH exome AF: 0.000281

GnomAD4 genome AF: 0.00192 AC: 293 AN: 152378 Hom.: 3 Cov.: 33 AF XY: 0.00199 AC XY: 148 AN XY: 74508

Gnomad4 AFR AF: 0.00656

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000867 Hom.: 0

Bravo AF: 0.00235

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 22, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 20, 2020	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	6.3
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs150541057; hg19: chr1-227149164;