17-58193522-C-T

Variant names:

• chr17-58193522-C-T
• rs149380205
• NM_000502.6:c.322C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000502.6(EPX):​c.322C>T​(p.Arg108Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: EPX NM_000502.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.173
• Publications: 1 publications found

Genes affected

EPX (HGNC:3423): (eosinophil peroxidase) This gene is a member of the peroxidase gene family and is expressed in eosinophils. The encoded preproprotein is proteolytically processed into covalently attached heavy and light chains to form the mature enzyme, which functions as an oxidant. The enzyme is released at sites of parasitic infection or allergen stimulation to mediate lysis of protozoa or parasitic worms. The gene is found in a gene cluster with other peroxidase genes on chromosome 17. Mutations in this gene result in eosinophil peroxidase deficiency. [provided by RefSeq, Feb 2016]

EPX Gene-Disease associations (from GenCC):

• eosinophil peroxidase deficiency

  Inheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0399985).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000502.6. 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
	EPX	NM_000502.6	MANE Select	c.322C>T	p.Arg108Trp	missense	Exon 3 of 13	NP_000493.1	P11678

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPX	ENST00000225371.6	TSL:2 MANE Select	c.322C>T	p.Arg108Trp	missense	Exon 3 of 13	ENSP00000225371.5	P11678

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251268 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000342 AC: 50 AN: 1461834 Hom.: 0 Cov.: 33 AF XY: 0.0000385 AC XY: 28 AN XY: 727224

African (AFR) AF: 0.000777 AC: 26 AN: 33478

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111984

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74356

African (AFR) AF: 0.000458 AC: 19 AN: 41442

American (AMR) AF: 0.000131 AC: 2 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.000155

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.073
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.74
DEOGEN2	Benign	0.27	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.032	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.17
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.056
Sift	Benign	0.21	T
Sift4G	Benign	0.19	T
Polyphen		0.0020	B
Vest4		0.18
MVP		0.41
MPC		0.12
ClinPred		0.0094	T
GERP RS		-0.84
Varity_R		0.037
gMVP		0.70
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs149380205; hg19: chr17-56270883; COSMIC: COSV56599226;