12-56267156-C-T

Variant names:

• chr12-56267156-C-T
• rs927403476
• NM_144576.4:c.38C>T

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.38C>T​(p.Thr13Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000724 in 1,188,194 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000072 (0 hom.)
• Consequence: COQ10A NM_144576.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.315
• Publications: 1 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]

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=0.18258965).

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.38C>T	p.Thr13Met	missense	Exon 1 of 5	NP_653177.3
	COQ10A	NM_001099337.2		c.-240C>T		upstream_gene	N/A	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.38C>T	p.Thr13Met	missense	Exon 1 of 5	ENSP00000312587.5	Q96MF6-1
	COQ10A	ENST00000925657.1		c.38C>T	p.Thr13Met	missense	Exon 1 of 5	ENSP00000595716.1
	COQ10A	ENST00000925658.1		c.38C>T	p.Thr13Met	missense	Exon 1 of 5	ENSP00000595717.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000724 AC: 86 AN: 1188194 Hom.: 0 Cov.: 31 AF XY: 0.0000555 AC XY: 32 AN XY: 576442

African (AFR) AF: 0.00 AC: 0 AN: 23470

American (AMR) AF: 0.00 AC: 0 AN: 10160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16294

East Asian (EAS) AF: 0.00 AC: 0 AN: 26936

South Asian (SAS) AF: 0.00 AC: 0 AN: 47332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3328

European-Non Finnish (NFE) AF: 0.0000874 AC: 86 AN: 984236

Other (OTH) AF: 0.00 AC: 0 AN: 48424

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.25
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.32
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.046
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.053	T
Polyphen		0.63	P
Vest4		0.16
MutPred		0.37		Loss of glycosylation at T13 (P = 0.0095)
MVP		0.40
MPC		0.28
ClinPred		0.29	T
GERP RS		3.0
PromoterAI		-0.36	Neutral
Varity_R		0.064
gMVP		0.47
Mutation Taster		=90/10	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

dbSNP: rs927403476; hg19: chr12-56660940;