chr9-128322868-C-A

Variant names:

• chr9-128322868-C-A
• rs757566504
• NM_016035.5:c.10C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016035.5(COQ4):​c.10C>A​(p.Leu4Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COQ4 NM_016035.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.077946186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ4	NM_016035.5	c.10C>A	p.Leu4Met	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.10C>A	p.Leu4Met	missense_variant	Exon 1 of 7	1	NM_016035.5	ENSP00000300452.3
COQ4	ENST00000372875.3	c.10C>A	p.Leu4Met	missense_variant	Exon 1 of 4	2		ENSP00000361966.3
COQ4	ENST00000608951.5	c.10C>A	p.Leu4Met	missense_variant	Exon 1 of 3	2		ENSP00000476323.1
COQ4	ENST00000609948.1	c.10C>A	p.Leu4Met	missense_variant	Exon 1 of 2	2		ENSP00000477292.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1421648 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 705110

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.: 33

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.6
DANN	Benign	0.73
DEOGEN2	Benign	0.0044	T;T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.40	T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.078	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;.;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.35	N;.;.;N
REVEL	Benign	0.069
Sift	Uncertain	0.018	D;.;.;D
Sift4G	Benign	0.072	T;T;D;T
Polyphen		0.44	B;.;.;P
Vest4		0.25
MVP		0.088
MPC		0.74
ClinPred		0.44	T
GERP RS		0.016
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.094
gMVP		0.51

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: rs757566504; hg19: chr9-131085147;