17-58193047-G-A

Variant names:

• chr17-58193047-G-A
• rs773020930
• NM_000502.6:c.86G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000502.6(EPX):​c.86G>A​(p.Gly29Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,458,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: EPX NM_000502.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.948

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.077598274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPX	NM_000502.6	c.86G>A	p.Gly29Glu	missense_variant	Exon 2 of 13	ENST00000225371.6	NP_000493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPX	ENST00000225371.6	c.86G>A	p.Gly29Glu	missense_variant	Exon 2 of 13	2	NM_000502.6	ENSP00000225371.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251474 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135914

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1458058 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 725718

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: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.86G>A (p.G29E) alteration is located in exon 2 (coding exon 2) of the EPX gene. This alteration results from a G to A substitution at nucleotide position 86, causing the glycine (G) at amino acid position 29 to be replaced by a glutamic acid (E). 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	0.064
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.78
DANN	Benign	0.51
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.14
Sift	Benign	0.32	T
Sift4G	Benign	0.57	T
Polyphen		0.0010	B
Vest4		0.076
MutPred		0.20		Gain of disorder (P = 0.0728);
MVP		0.61
MPC		0.15
ClinPred		0.044	T
GERP RS		3.9
Varity_R		0.039
gMVP		0.29

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: rs773020930; hg19: chr17-56270408; COSMIC: COSV56599714;