chr12-56267156-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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

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=0.18258965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ10A	NM_144576.4	c.38C>T	p.Thr13Met	missense_variant	Exon 1 of 5	ENST00000308197.10	NP_653177.3
COQ10A	NM_001099337.2	c.-240C>T		upstream_gene_variant			NP_001092807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ10A	ENST00000308197.10	c.38C>T	p.Thr13Met	missense_variant	Exon 1 of 5	1	NM_144576.4	ENSP00000312587.5

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

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: 0.0000874

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.38C>T (p.T13M) alteration is located in exon 1 (coding exon 1) of the COQ10A gene. This alteration results from a C to T substitution at nucleotide position 38, causing the threonine (T) at amino acid position 13 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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
Varity_R		0.064
gMVP		0.47

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: rs927403476; hg19: chr12-56660940;