12-120522299-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_032314.4(COQ5):c.267T>C(p.Gly89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,613,640 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (16 hom.)
• Consequence: COQ5 NM_032314.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.536

Genes affected

COQ5 (HGNC:28722): (coenzyme Q5, methyltransferase) Enables 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase activity. Involved in methylation and ubiquinone biosynthetic process. Located in mitochondrial matrix. Part of protein-containing complex. Colocalizes with mitochondrial inner membrane. Implicated in primary coenzyme Q10 deficiency 9. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 12-120522299-A-G is Benign according to our data. Variant chr12-120522299-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1335120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.536 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ5	NM_032314.4	c.267T>C	p.Gly89=	synonymous_variant	2/7	ENST00000288532.11
COQ5	XM_006719639.3	c.24T>C	p.Gly8=	synonymous_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ5	ENST00000288532.11	c.267T>C	p.Gly89=	synonymous_variant	2/7	1	NM_032314.4	P1

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 374 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00285

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00291 AC: 732 AN: 251476 Hom.: 5 AF XY: 0.00285 AC XY: 388 AN XY: 135920

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00137

Gnomad FIN exome AF: 0.0138

Gnomad NFE exome AF: 0.00305

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00206 AC: 3011 AN: 1461344 Hom.: 16 Cov.: 31 AF XY: 0.00212 AC XY: 1541 AN XY: 727010

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.000919

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00137

Gnomad4 FIN exome AF: 0.0140

Gnomad4 NFE exome AF: 0.00179

Gnomad4 OTH exome AF: 0.00185

GnomAD4 genome AF: 0.00246 AC: 374 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.00298 AC XY: 222 AN XY: 74466

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0151

Gnomad4 NFE AF: 0.00285

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00258 Hom.: 1

Bravo AF: 0.00113

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00202

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

COQ5: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	5.9
Dann	Benign	0.67
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: rs142784328; hg19: chr12-120960102;