dbSNP rs7208693: MPO:p.Val53Phe (chr17-58280457-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000250.2(MPO):c.157G>T(p.Val53Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 1,613,748 control chromosomes in the GnomAD database, including 6,252 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1082 hom., cov: 32)

Exomes 𝑓: 0.079 ( 5170 hom. )

Consequence

MPO
NM_000250.2 missense, splice_region

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0440

Variant links:

Genes affected

MPO (HGNC:7218): (myeloperoxidase) Myeloperoxidase (MPO) is a heme protein synthesized during myeloid differentiation that constitutes the major component of neutrophil azurophilic granules. Produced as a single chain precursor, myeloperoxidase is subsequently cleaved into a light and heavy chain. The mature myeloperoxidase is a tetramer composed of 2 light chains and 2 heavy chains. This enzyme produces hypohalous acids central to the microbicidal activity of neutrophils. [provided by RefSeq, Nov 2014]

MPO links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012850165).

BP6

Variant 17-58280457-C-A is Benign according to our data. Variant chr17-58280457-C-A is described in ClinVar as [Benign]. Clinvar id is 3055447.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-58280457-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPO	NM_000250.2 link	c.157G>T	p.Val53Phe	missense_variant, splice_region_variant	Exon 2 of 12	ENST00000225275.4	NP_000241.1	P05164-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPO	ENST00000225275.4 link	c.157G>T	p.Val53Phe	missense_variant, splice_region_variant	Exon 2 of 12	1	NM_000250.2	ENSP00000225275.3		P05164-1
MPO	ENST00000580005.1 link	n.86G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16466

AN:

152042

Hom.:

1078

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.0835

Gnomad AMR

AF:

0.0679

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.0860

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0758

Gnomad OTH

AF:

0.0860

GnomAD3 exomes

AF:

0.0895

AC:

22421

AN:

250438

Hom.:

1208

AF XY:

0.0851

AC XY:

11528

AN XY:

135414

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.0855

Gnomad ASJ exome

AF:

0.0331

Gnomad EAS exome

AF:

0.125

Gnomad SAS exome

AF:

0.0818

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.0732

Gnomad OTH exome

AF:

0.0720

GnomAD4 exome

AF:

0.0786

AC:

114847

AN:

1461586

Hom.:

5170

Cov.:

AF XY:

0.0775

AC XY:

56331

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.0838

Gnomad4 ASJ exome

AF:

0.0333

Gnomad4 EAS exome

AF:

0.126

Gnomad4 SAS exome

AF:

0.0789

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.0728

Gnomad4 OTH exome

AF:

0.0765

GnomAD4 genome

AF:

0.108

AC:

16491

AN:

152162

Hom.:

1082

Cov.:

AF XY:

0.109

AC XY:

8136

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.0686

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.0859

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.0758

Gnomad4 OTH

AF:

0.0865

Alfa

AF:

0.0709

Hom.:

956

Bravo

AF:

0.108

TwinsUK

AF:

0.0750

AC:

278

ALSPAC

AF:

0.0714

AC:

275

ESP6500AA

AF:

0.184

AC:

812

ESP6500EA

AF:

0.0726

AC:

624

ExAC

AF:

0.0913

AC:

11080

Asia WGS

AF:

0.114

AC:

395

AN:

3478

EpiCase

AF:

0.0604

EpiControl

AF:

0.0639

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MPO-related disorder

Benign:1

Jan 02, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

3.8

DANN

Benign

0.97

DEOGEN2

Benign

0.26

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.72

REVEL

Benign

0.072

Sift

Benign

0.25

Sift4G

Benign

0.45

Polyphen

0.086

Vest4

0.12

MPC

0.46

ClinPred

0.0018

GERP RS

-1.8

Varity_R

0.077

gMVP

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over