NM_020247.5:c.948C>T

Variant names:

• chr1-226982902-C-T
• rs55637780
• NM_020247.5:c.948C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020247.5(COQ8A):​c.948C>T​(p.Leu316Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,612,792 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 34)
  • Exomes 𝑓: 0.0023 (7 hom.)
• Consequence: COQ8A NM_020247.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.446
• Publications: 3 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-226982902-C-T is Benign according to our data. Variant chr1-226982902-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.446 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00217 (330/152352) while in subpopulation AMR AF = 0.00346 (53/15310). AF 95% confidence interval is 0.00272. There are 2 homozygotes in GnomAd4. There are 156 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.948C>T	p.Leu316Leu	synonymous	Exon 8 of 15	NP_064632.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ8A	ENST00000366777.4	TSL:1 MANE Select	c.948C>T	p.Leu316Leu	synonymous	Exon 8 of 15	ENSP00000355739.3	Q8NI60-1
	COQ8A	ENST00000366778.5	TSL:1	c.792C>T	p.Leu264Leu	synonymous	Exon 8 of 15	ENSP00000355740.1	Q8NI60-3
	ENSG00000288674	ENST00000366779.6	TSL:2	n.*5675C>T		non_coding_transcript_exon	Exon 25 of 32	ENSP00000355741.2

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 329 AN: 152234 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00284

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00218 AC: 542 AN: 248836 AF XY: 0.00245

Gnomad AFR exome AF: 0.000188

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00219

Gnomad NFE exome AF: 0.00265

Gnomad OTH exome AF: 0.00280

GnomAD4 exome AF: 0.00230 AC: 3359 AN: 1460440 Hom.: 7 Cov.: 34 AF XY: 0.00232 AC XY: 1683 AN XY: 726496

African (AFR) AF: 0.000209 AC: 7 AN: 33470

American (AMR) AF: 0.00175 AC: 78 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00995 AC: 260 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.000997 AC: 86 AN: 86234

European-Finnish (FIN) AF: 0.00256 AC: 134 AN: 52272

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5752

European-Non Finnish (NFE) AF: 0.00237 AC: 2632 AN: 1111848

Other (OTH) AF: 0.00253 AC: 153 AN: 60374

GnomAD4 genome AF: 0.00217 AC: 330 AN: 152352 Hom.: 2 Cov.: 34 AF XY: 0.00209 AC XY: 156 AN XY: 74502

African (AFR) AF: 0.000264 AC: 11 AN: 41588

American (AMR) AF: 0.00346 AC: 53 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00284 AC: 193 AN: 68038

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00247 Hom.: 0

Bravo AF: 0.00193

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00393

EpiControl AF: 0.00320

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not provided (6)
-	-	1	COQ8A-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs55637780; hg19: chr1-227170603;