NM_001297732.2:c.937T>A

Variant names:

• chr4-73058182-A-T
• NM_001297732.2:c.937T>A

Variant summary

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

The NM_001297732.2(COX18):​c.937T>A​(p.Ser313Thr) 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. 14/20 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: COX18 NM_001297732.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32
• Publications: 0 publications found

Genes affected

COX18 (HGNC:26801): (cytochrome c oxidase assembly factor COX18) This gene encodes a cytochrome c oxidase assembly protein. The encoded protein is essential for integral membrane protein insertion into the mitochondrial inner membrane. It is also required for cytochrome c oxidase assembly and activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

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=0.1279166).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297732.2. 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
	COX18	NM_001297732.2	MANE Select	c.937T>A	p.Ser313Thr	missense	Exon 6 of 6	NP_001284661.1	B7ZL88
	COX18	NM_001300729.1		c.943T>A	p.Ser315Thr	missense	Exon 5 of 5	NP_001287658.1	Q8N8Q8
	COX18	NM_173827.4		c.934T>A	p.Ser312Thr	missense	Exon 6 of 6	NP_776188.1	Q8N8Q8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX18	ENST00000507544.3	TSL:1 MANE Select	c.937T>A	p.Ser313Thr	missense	Exon 6 of 6	ENSP00000425261.3	B7ZL88
	COX18	ENST00000295890.8	TSL:1	c.934T>A	p.Ser312Thr	missense	Exon 6 of 6	ENSP00000295890.4	Q8N8Q8-1
	COX18	ENST00000449739.6	TSL:1	n.*443T>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000394583.2	Q8N8Q8-3

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	0.071
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.019
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.65	T
PhyloP100		4.3
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.073
Sift	Benign	0.20	T
Sift4G	Benign	0.23	T
Polyphen		0.059	B
Vest4		0.17
MutPred		0.27		Gain of glycosylation at T317 (P = 0.0072)
MVP		0.43
MPC		0.29
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.18
gMVP		0.56
Mutation Taster		=82/18	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: chr4-73923899;