9-128322875-G-T

Variant names:

• chr9-128322875-G-T
• rs371409929
• NM_016035.5:c.17G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016035.5(COQ4):​c.17G>T​(p.Arg6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,429,302 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COQ4 NM_016035.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05012998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ4	NM_016035.5	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 7	ENST00000300452.8	NP_057119.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ4	ENST00000300452.8	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 7	1	NM_016035.5	ENSP00000300452.3
COQ4	ENST00000372875.3	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 4	2		ENSP00000361966.3
COQ4	ENST00000608951.5	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 3	2		ENSP00000476323.1
COQ4	ENST00000609948.1	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 2	2		ENSP00000477292.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1429302 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 709546

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: 9.09e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.8
DANN	Benign	0.57
DEOGEN2	Benign	0.0043	T;T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.46	T;T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.050	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.51	N;.;.;N
REVEL	Benign	0.0050
Sift	Benign	0.40	T;.;.;T
Sift4G	Benign	0.32	T;D;D;D
Polyphen		0.0	B;.;.;B
Vest4		0.096
MutPred		0.41		Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);
MVP		0.076
MPC		0.49
ClinPred		0.037	T
GERP RS		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.056
gMVP		0.46

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: rs371409929; hg19: chr9-131085154;