12-56270253-C-G

Variant names:

• chr12-56270253-C-G
• NM_144576.4:c.680C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144576.4(COQ10A):​c.680C>G​(p.Thr227Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COQ10A NM_144576.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.51
• Publications: 0 publications found

Genes affected

COQ10A (HGNC:26515): (coenzyme Q10A) Predicted to enable ubiquinone binding activity. Predicted to be involved in cellular respiration and ubiquinone biosynthetic process. Predicted to be located in mitochondrial inner membrane. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258260 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0820438).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144576.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ10A	NM_144576.4	MANE Select	c.680C>G	p.Thr227Ser	missense	Exon 5 of 5	NP_653177.3
	COQ10A	NM_001099337.2		c.584C>G	p.Thr195Ser	missense	Exon 5 of 5	NP_001092807.1	Q96MF6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ10A	ENST00000308197.10	TSL:1 MANE Select	c.680C>G	p.Thr227Ser	missense	Exon 5 of 5	ENSP00000312587.5	Q96MF6-1
	COQ10A	ENST00000546544.5	TSL:1	c.629C>G	p.Thr210Ser	missense	Exon 4 of 4	ENSP00000446723.1	Q96MF6-2
	COQ10A	ENST00000433805.6	TSL:1	c.584C>G	p.Thr195Ser	missense	Exon 5 of 5	ENSP00000407843.2	Q96MF6-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Benign	0.87
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.42	N
PhyloP100		5.5
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.087
Sift	Benign	0.23	T
Sift4G	Benign	0.31	T
Polyphen		0.0060	B
Vest4		0.084
MutPred		0.28		Gain of glycosylation at T227 (P = 0.0504)
MVP		0.20
MPC		0.25
ClinPred		0.33	T
GERP RS		3.9
Varity_R		0.16
gMVP		0.22
Mutation Taster		=83/17	polymorphism

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

hg19: chr12-56664037;