chr12-50120159-A-G

Position:

• chr12-50120159-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032901.4(COX14):​c.116A>G​(p.Gln39Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COX14 NM_032901.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.25

Genes affected

COX14 (HGNC:28216): (cytochrome c oxidase assembly factor COX14) This gene encodes a small single-pass transmembrane protein that localizes to mitochondria. This protein may play a role in coordinating the early steps of cytochrome c oxidase (COX; also known as complex IV) subunit assembly and, in particular, the synthesis and assembly of the COX I subunit of the holoenzyme. Mutations in this gene have been associated with mitochondrial complex IV deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ENSG00000272368 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31858614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX14	NM_032901.4	c.116A>G	p.Gln39Arg	missense_variant	2/2	ENST00000550487.6	NP_116290.1
COX14	NM_001257133.2	c.116A>G	p.Gln39Arg	missense_variant	3/3		NP_001244062.1
COX14	NM_001257134.2	c.116A>G	p.Gln39Arg	missense_variant	2/2		NP_001244063.1
COX14	XM_047429769.1	c.116A>G	p.Gln39Arg	missense_variant	3/3		XP_047285725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX14	ENST00000550487.6	c.116A>G	p.Gln39Arg	missense_variant	2/2	1	NM_032901.4	ENSP00000446524.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.116A>G (p.Q39R) alteration is located in exon 2 (coding exon 1) of the COX14 gene. This alteration results from a A to G substitution at nucleotide position 116, causing the glutamine (Q) at amino acid position 39 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	0.10
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;T;T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.32	.;.;.;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Uncertain	-0.059	T
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.019	D;D;D;D
Sift4G	Uncertain	0.031	D;D;D;D
Polyphen		0.86	P;P;P;P
Vest4		0.21
MutPred		0.30		Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);
MVP		0.63
MPC		0.54
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.31
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr12-50513942;