17-58193064-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000502.6(EPX):c.103G>A(p.Val35Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000796 in 1,613,374 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0042 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (5 hom.)
• Consequence: EPX NM_000502.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.21

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006103128).
• BP6: Variant 17-58193064-G-A is Benign according to our data. Variant chr17-58193064-G-A is described in ClinVar as [Benign]. Clinvar id is 720759.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPX	NM_000502.6	c.103G>A	p.Val35Ile	missense_variant	2/13	ENST00000225371.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPX	ENST00000225371.6	c.103G>A	p.Val35Ile	missense_variant	2/13	2	NM_000502.6	P1

Frequencies

GnomAD3 genomes AF: 0.00422 AC: 642 AN: 152162 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

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: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00118 AC: 298 AN: 251482 Hom.: 3 AF XY: 0.000942 AC XY: 128 AN XY: 135916

Gnomad AFR exome AF: 0.0155

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000437 AC: 639 AN: 1461094 Hom.: 5 Cov.: 31 AF XY: 0.000369 AC XY: 268 AN XY: 726962

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000270

Gnomad4 OTH exome AF: 0.00101

GnomAD4 genome AF: 0.00424 AC: 646 AN: 152280 Hom.: 9 Cov.: 32 AF XY: 0.00400 AC XY: 298 AN XY: 74472

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000983 Hom.: 2

Bravo AF: 0.00505

ESP6500AA AF: 0.0104 AC: 46

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00139 AC: 169

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	14
Dann	Benign	0.97
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0061	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.16
Sift	Benign	0.59	T
Sift4G	Benign	0.45	T
Polyphen		0.038	B
Vest4		0.12
MVP		0.56
MPC		0.10
ClinPred		0.027	T
GERP RS		5.1
Varity_R		0.031
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs34553736; hg19: chr17-56270425;