rs3003601

chr9-128323094-G-Achr9-128323094-G-Cchr9-128323094-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1 BP4_Moderate

The NM_016035.5(COQ4):c.149G>A(p.Gly50Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G50A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COQ4 NM_016035.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

Genes affected

COQ4 (HGNC:19693): (coenzyme Q4) This gene encodes a component of the coenzyme Q biosynthesis pathway. Coenzyme Q, an essential component of the electron transport chain, shuttles electrons between complexes I or II to complex III of the mitochondrial transport chain. This protein appears to play a structural role in stabilizing a complex that contains most of the coenzyme Q biosynthesis enzymes. Mutations in this gene are associated with mitochondrial disorders linked to coenzyme Q deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM1: In a chain Ubiquinone biosynthesis protein COQ4 homolog, mitochondrial (size 234) in uniprot entity COQ4_HUMAN there are 48 pathogenic changes around while only 10 benign (83%) in NM_016035.5
• BP4: Computational evidence support a benign effect (MetaRNN=0.108132124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ4	NM_016035.5	c.149G>A	p.Gly50Glu	missense_variant	2/7	ENST00000300452.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ4	ENST00000300452.8	c.149G>A	p.Gly50Glu	missense_variant	2/7	1	NM_016035.5	P1
COQ4	ENST00000372875.3	c.149G>A	p.Gly50Glu	missense_variant	2/4	2
COQ4	ENST00000608951.5	c.149G>A	p.Gly50Glu	missense_variant	2/3	2
COQ4	ENST00000609948.1	c.149G>A	p.Gly50Glu	missense_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1459538 Hom.: 0 Cov.: 63 AF XY: 0.00 AC XY: 0 AN XY: 726160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	18
Dann	Benign	0.97
DEOGEN2	Benign	0.21	T;D;.;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.64	T;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.78	N;.;.;N
REVEL	Benign	0.046
Sift	Benign	0.052	T;.;.;T
Sift4G	Benign	0.43	T;T;T;D
Polyphen		0.049	B;.;.;P
Vest4		0.17
MutPred		0.65		Loss of catalytic residue at P46 (P = 0.0829);Loss of catalytic residue at P46 (P = 0.0829);Loss of catalytic residue at P46 (P = 0.0829);Loss of catalytic residue at P46 (P = 0.0829);
MVP		0.14
MPC		0.53
ClinPred		0.30	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.33
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3003601; hg19: chr9-131085373;