NM_001347969.2:c.1435G>C

Variant names:

• chr13-43298357-C-G
• rs138978304
• NM_001347969.2:c.1435G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001347969.2(ENOX1):​c.1435G>C​(p.Gly479Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000926 in 1,608,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00067 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (0 hom.)
• Consequence: ENOX1 NM_001347969.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13687345).

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.1435G>C	p.Gly479Arg	missense	Exon 12 of 17	NP_001334898.1	A0A024RDT8
	ENOX1	NM_001347963.2		c.1540G>C	p.Gly514Arg	missense	Exon 11 of 16	NP_001334892.1
	ENOX1	NM_001127615.3		c.1435G>C	p.Gly479Arg	missense	Exon 12 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.1435G>C	p.Gly479Arg	missense	Exon 12 of 17	ENSP00000509229.1	Q8TC92-1
	ENOX1	ENST00000261488.10	TSL:1	c.1435G>C	p.Gly479Arg	missense	Exon 12 of 17	ENSP00000261488.6	Q8TC92-1
	ENOX1	ENST00000871211.1		c.1435G>C	p.Gly479Arg	missense	Exon 13 of 18	ENSP00000541270.1

Frequencies

GnomAD3 genomes AF: 0.000672 AC: 101 AN: 150396 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000199

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000564 AC: 140 AN: 248292 AF XY: 0.000640

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.000526

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000468

Gnomad NFE exome AF: 0.00102

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.000952 AC: 1388 AN: 1458048 Hom.: 0 Cov.: 35 AF XY: 0.000931 AC XY: 675 AN XY: 725224

African (AFR) AF: 0.000121 AC: 4 AN: 33094

American (AMR) AF: 0.000518 AC: 23 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85416

European-Finnish (FIN) AF: 0.0000753 AC: 4 AN: 53110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00118 AC: 1315 AN: 1110518

Other (OTH) AF: 0.000681 AC: 41 AN: 60210

GnomAD4 genome AF: 0.000672 AC: 101 AN: 150396 Hom.: 0 Cov.: 33 AF XY: 0.000642 AC XY: 47 AN XY: 73240

African (AFR) AF: 0.000170 AC: 7 AN: 41078

American (AMR) AF: 0.000199 AC: 3 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00134 AC: 91 AN: 67772

Other (OTH) AF: 0.00 AC: 0 AN: 2058

Alfa AF: 0.000863 Hom.: 1

Bravo AF: 0.000680

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.000453 AC: 55

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	0.69
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.8
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.060
Sift	Benign	0.068	T
Sift4G	Uncertain	0.011	D
Polyphen		0.42	B
Vest4		0.63
MVP		0.26
MPC		1.0
ClinPred		0.066	T
GERP RS		4.9
Varity_R		0.42
gMVP		0.25
Mutation Taster		=91/9	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

dbSNP: rs138978304; hg19: chr13-43872493; COSMIC: COSV54899396;