13-43298513-A-G

Position:

• chr13-43298513-A-G

Variant summary

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

The NM_001347969.2(ENOX1):​c.1279T>C​(p.Tyr427His) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,104 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ENOX1 NM_001347969.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49

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

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=0.2718024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOX1	NM_001347969.2	c.1279T>C	p.Tyr427His	missense_variant	12/17	ENST00000690772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOX1	ENST00000690772.1	c.1279T>C	p.Tyr427His	missense_variant	12/17		NM_001347969.2	P1
ENOX1	ENST00000261488.10	c.1279T>C	p.Tyr427His	missense_variant	12/17	1		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460104 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726254

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

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

Apr 12, 2023

The c.1279T>C (p.Y427H) alteration is located in exon 12 (coding exon 9) of the ENOX1 gene. This alteration results from a T to C substitution at nucleotide position 1279, causing the tyrosine (Y) at amino acid position 427 to be replaced by a histidine (H). 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	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.11
Sift	Benign	0.11	T
Sift4G	Benign	0.17	T
Polyphen		0.98	D
Vest4		0.34
MutPred		0.21		Loss of phosphorylation at Y427 (P = 0.0522);
MVP		0.68
MPC		0.98
ClinPred		0.63	D
GERP RS		5.6
Varity_R		0.14
gMVP		0.099

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-43872649;