13-43298510-C-A

Variant names:

• chr13-43298510-C-A
• rs776535217
• NM_001347969.2:c.1282G>T

Variant summary

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

The NM_001347969.2(ENOX1):​c.1282G>T​(p.Ala428Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A428T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ENOX1 NM_001347969.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75
• Publications: 2 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17630202).

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.1282G>T	p.Ala428Ser	missense	Exon 12 of 17	NP_001334898.1	A0A024RDT8
	ENOX1	NM_001347963.2		c.1387G>T	p.Ala463Ser	missense	Exon 11 of 16	NP_001334892.1
	ENOX1	NM_001127615.3		c.1282G>T	p.Ala428Ser	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.1282G>T	p.Ala428Ser	missense	Exon 12 of 17	ENSP00000509229.1	Q8TC92-1
	ENOX1	ENST00000261488.10	TSL:1	c.1282G>T	p.Ala428Ser	missense	Exon 12 of 17	ENSP00000261488.6	Q8TC92-1
	ENOX1	ENST00000871211.1		c.1282G>T	p.Ala428Ser	missense	Exon 13 of 18	ENSP00000541270.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250644 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460708 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726588

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 85994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5396

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111716

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.083
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.74	N
PhyloP100		5.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.048
Sift	Benign	0.21	T
Sift4G	Benign	0.37	T
Polyphen		0.0010	B
Vest4		0.48
MutPred		0.15		Gain of phosphorylation at A428 (P = 0.0497)
MVP		0.60
MPC		1.5
ClinPred		0.87	D
GERP RS		4.8
Varity_R		0.17
gMVP		0.055
Mutation Taster		=88/12	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: rs776535217; hg19: chr13-43872646;