11-73873359-T-C

Variant names:

• chr11-73873359-T-C
• NM_016565.3:c.20A>G

Variant summary

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

The NM_016565.3(COA4):​c.20A>G​(p.Gln7Arg) 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. 13/19 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: COA4 NM_016565.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

Genes affected

COA4 (HGNC:24604): (cytochrome c oxidase assembly factor 4 homolog) Predicted to be involved in mitochondrial cytochrome c oxidase assembly. Located 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=0.09043589).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COA4	NM_016565.3	c.20A>G	p.Gln7Arg	missense_variant	Exon 2 of 2	ENST00000355693.5	NP_057649.2
COA4	XM_017017883.2	c.47A>G	p.Gln16Arg	missense_variant	Exon 2 of 2		XP_016873372.1
COA4	XM_017017884.2	c.20A>G	p.Gln7Arg	missense_variant	Exon 3 of 3		XP_016873373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COA4	ENST00000355693.5	c.20A>G	p.Gln7Arg	missense_variant	Exon 2 of 2	1	NM_016565.3	ENSP00000347919.4
COA4	ENST00000541455.1	c.47A>G	p.Gln16Arg	missense_variant	Exon 2 of 2	5		ENSP00000440756.1
COA4	ENST00000537289.1	c.20A>G	p.Gln7Arg	missense_variant	Exon 3 of 3	2		ENSP00000437772.1
COA4	ENST00000545127.1	c.20A>G	p.Gln7Arg	missense_variant	Exon 2 of 2	2		ENSP00000443795.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.20A>G (p.Q7R) alteration is located in exon 2 (coding exon 1) of the COA4 gene. This alteration results from a A to G substitution at nucleotide position 20, causing the glutamine (Q) at amino acid position 7 to be replaced by an arginine (R). 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	0.069
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0062	T;T;.;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.33	.;.;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.090	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.59	N;N;N;N
REVEL	Benign	0.026
Sift	Benign	0.055	T;T;D;T
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.011	B;B;.;B
Vest4		0.076
MutPred		0.20		Gain of MoRF binding (P = 0.0021);Gain of MoRF binding (P = 0.0021);.;Gain of MoRF binding (P = 0.0021);
MVP		0.18
MPC		0.16
ClinPred		0.66	D
GERP RS		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.074
gMVP		0.091

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-73584404;