rs3742049

Variant names:

• chr12-120516687-C-T
• rs3742049
• NM_032314.4:c.454G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032314.4(COQ5):​c.454G>A​(p.Ala152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,768 control chromosomes in the GnomAD database, including 11,549 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1951 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9598 hom.)
• Consequence: COQ5 NM_032314.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328
• Publications: 31 publications found

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]

COQ5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P
• coenzyme q10 deficiency, primary, 9

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016256571).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ5	NM_032314.4	c.454G>A	p.Ala152Thr	missense_variant	Exon 3 of 7	ENST00000288532.11	NP_115690.3
COQ5	XM_006719639.3	c.211G>A	p.Ala71Thr	missense_variant	Exon 4 of 8		XP_006719702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ5	ENST00000288532.11	c.454G>A	p.Ala152Thr	missense_variant	Exon 3 of 7	1	NM_032314.4	ENSP00000288532.6

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22370 AN: 151966 Hom.: 1940 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.0682

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.117

GnomAD2 exomes AF: 0.114 AC: 28584 AN: 251496 AF XY: 0.109

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.0690

Gnomad EAS exome AF: 0.0659

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.0940

GnomAD4 exome AF: 0.110 AC: 161033 AN: 1461684 Hom.: 9598 Cov.: 33 AF XY: 0.109 AC XY: 79029 AN XY: 727144

African (AFR) AF: 0.253 AC: 8476 AN: 33472

American (AMR) AF: 0.108 AC: 4812 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 1696 AN: 26134

East Asian (EAS) AF: 0.0681 AC: 2702 AN: 39698

South Asian (SAS) AF: 0.0785 AC: 6771 AN: 86242

European-Finnish (FIN) AF: 0.127 AC: 6798 AN: 53414

Middle Eastern (MID) AF: 0.0982 AC: 566 AN: 5766

European-Non Finnish (NFE) AF: 0.110 AC: 122732 AN: 1111844

Other (OTH) AF: 0.107 AC: 6480 AN: 60390

GnomAD4 genome AF: 0.147 AC: 22423 AN: 152084 Hom.: 1951 Cov.: 32 AF XY: 0.146 AC XY: 10859 AN XY: 74362

African (AFR) AF: 0.245 AC: 10136 AN: 41446

American (AMR) AF: 0.122 AC: 1868 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3472

East Asian (EAS) AF: 0.0683 AC: 354 AN: 5182

South Asian (SAS) AF: 0.0778 AC: 374 AN: 4806

European-Finnish (FIN) AF: 0.132 AC: 1395 AN: 10594

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7764 AN: 68002

Other (OTH) AF: 0.116 AC: 245 AN: 2106

Alfa AF: 0.118 Hom.: 3799

Bravo AF: 0.148

TwinsUK AF: 0.102 AC: 378

ALSPAC AF: 0.110 AC: 425

ESP6500AA AF: 0.252 AC: 1112

ESP6500EA AF: 0.108 AC: 927

ExAC AF: 0.118 AC: 14379

Asia WGS AF: 0.108 AC: 377 AN: 3478

EpiCase AF: 0.106

EpiControl AF: 0.105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T;T;T;T
Eigen	Benign	-0.044
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.74	T;T;T;T
MetaRNN	Benign	0.0016	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PhyloP100		0.33
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.53	N;N;N;N
REVEL	Benign	0.048
Sift	Benign	0.25	T;T;T;T
Sift4G	Benign	0.15	T;.;T;.
Polyphen		0.051	B;.;.;.
Vest4		0.022
MPC		0.20
ClinPred		0.014	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.030
gMVP		0.55
Mutation Taster		=88/12	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3742049; hg19: chr12-120954490; COSMIC: COSV56019122; COSMIC: COSV56019122;