chr13-43344627-C-G

Variant names:

• chr13-43344627-C-G
• rs150644099
• NM_001347969.2:c.947G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001347969.2(ENOX1):​c.947G>C​(p.Arg316Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENOX1 NM_001347969.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

ENOX1 (HGNC:25474): (ecto-NOX disulfide-thiol exchanger 1) The protein encoded by this gene is involved in plasma membrane electron transport pathways. The encoded protein has both a hydroquinone (NADH) oxidase activity and a protein disulfide-thiol interchange activity. The two activities cycle with a periodicity of 24 minutes, with one activity being at its peak when the other is at its lowest. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347969.2. 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
	ENOX1	NM_001347969.2	MANE Select	c.947G>C	p.Arg316Pro	missense	Exon 9 of 17	NP_001334898.1	A0A024RDT8
	ENOX1	NM_001347963.2		c.1052G>C	p.Arg351Pro	missense	Exon 8 of 16	NP_001334892.1
	ENOX1	NM_001127615.3		c.947G>C	p.Arg316Pro	missense	Exon 9 of 17	NP_001121087.1	A0A024RDT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOX1	ENST00000690772.1	MANE Select	c.947G>C	p.Arg316Pro	missense	Exon 9 of 17	ENSP00000509229.1	Q8TC92-1
	ENOX1	ENST00000261488.10	TSL:1	c.947G>C	p.Arg316Pro	missense	Exon 9 of 17	ENSP00000261488.6	Q8TC92-1
	ENOX1	ENST00000871211.1		c.947G>C	p.Arg316Pro	missense	Exon 10 of 18	ENSP00000541270.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.37		Gain of catalytic residue at V314 (P = 0.0013)
MVP		0.57
MPC		1.7
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.92
gMVP		0.88
Mutation Taster		=18/82	disease causing

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: rs150644099; hg19: chr13-43918763;