chr17-58194001-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000502.6(EPX):​c.503C>T​(p.Ala168Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.8e-7 ( 0 hom. )

Consequence

EPX
NM_000502.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.907
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.4065129).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EPXNM_000502.6 linkc.503C>T p.Ala168Val missense_variant Exon 5 of 13 ENST00000225371.6 NP_000493.1 P11678

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EPXENST00000225371.6 linkc.503C>T p.Ala168Val missense_variant Exon 5 of 13 2 NM_000502.6 ENSP00000225371.5 P11678

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460784
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
726746
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 13, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.503C>T (p.A168V) alteration is located in exon 5 (coding exon 5) of the EPX gene. This alteration results from a C to T substitution at nucleotide position 503, causing the alanine (A) at amino acid position 168 to be replaced by a valine (V). 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
0.10
BayesDel_addAF
Benign
-0.042
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
13
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
T
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.47
N
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.41
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.3
L
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.22
Sift
Benign
0.11
T
Sift4G
Benign
0.24
T
Polyphen
0.24
B
Vest4
0.22
MVP
0.60
MPC
0.14
ClinPred
0.70
D
GERP RS
3.0
Varity_R
0.13
gMVP
0.63

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: chr17-56271362; API