Genetic Variant NM_000250.2:c.2174G>C (chr17-58270720-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_000250.2(MPO):c.2174G>C(p.Arg725Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R725Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

MPO
NM_000250.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.614

Publications

3 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30238444).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000250.2. 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
	MPO	NM_000250.2	MANE Select	c.2174G>C	p.Arg725Pro	missense	Exon 12 of 12	NP_000241.1	P05164-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPO	ENST00000225275.4	TSL:1 MANE Select	c.2174G>C	p.Arg725Pro	missense	Exon 12 of 12	ENSP00000225275.3	P05164-1
MPO	ENST00000578493.2	TSL:3	n.1507G>C		non_coding_transcript_exon	Exon 7 of 7
MPO	ENST00000699291.1		n.*723G>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000514272.1	A0A8V8TPE5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000398

AC:

AN:

251022

AF XY:

0.0000589

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000336

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111990

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000412

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.68

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.61

M_CAP

Benign

0.075

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.9

PhyloP100

-0.61

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.25

Sift

Benign

0.051

Sift4G

Benign

0.18

Polyphen

0.78

Vest4

0.34

MutPred

0.43

Loss of stability (P = 0.0792)

MVP

0.85

MPC

0.84

ClinPred

0.50

GERP RS

1.2

Varity_R

0.89

gMVP

0.83

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over