NM_000250.2:c.2047G>C

Variant names:

• chr17-58270847-C-G
• rs35702888
• NM_000250.2:c.2047G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_000250.2(MPO):​c.2047G>C​(p.Glu683Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000477 in 1,613,310 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (5 hom.)
• Consequence: MPO NM_000250.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -0.618
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0042060018).
• BS2: High Homozygotes in GnomAdExome4 at 5 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.2047G>C	p.Glu683Gln	missense	Exon 12 of 12	NP_000241.1	P05164-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPO	ENST00000225275.4	TSL:1 MANE Select	c.2047G>C	p.Glu683Gln	missense	Exon 12 of 12	ENSP00000225275.3	P05164-1
	MPO	ENST00000577220.1	TSL:3	c.184-42G>C		intron	N/A	ENSP00000464668.1	J3QSF7
	MPO	ENST00000578493.2	TSL:3	n.1380G>C		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 374 AN: 152180 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00874

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

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: 0.000478

GnomAD2 exomes AF: 0.000613 AC: 154 AN: 251266 AF XY: 0.000405

Gnomad AFR exome AF: 0.00837

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000271 AC: 396 AN: 1461012 Hom.: 5 Cov.: 30 AF XY: 0.000222 AC XY: 161 AN XY: 726818

African (AFR) AF: 0.00981 AC: 328 AN: 33450

American (AMR) AF: 0.000447 AC: 20 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000198 AC: 1 AN: 5058

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1112002

Other (OTH) AF: 0.000630 AC: 38 AN: 60314

GnomAD4 genome AF: 0.00246 AC: 374 AN: 152298 Hom.: 1 Cov.: 32 AF XY: 0.00226 AC XY: 168 AN XY: 74472

African (AFR) AF: 0.00871 AC: 362 AN: 41554

American (AMR) AF: 0.000588 AC: 9 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.00273

ESP6500AA AF: 0.00794 AC: 35

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000700 AC: 85

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.8
DANN	Benign	0.78
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.62
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.14
Sift	Benign	0.13	T
Sift4G	Benign	0.12	T
Polyphen		0.0	B
Vest4		0.036
MVP		0.37
MPC		0.34
ClinPred		0.0011	T
GERP RS		-5.5
Varity_R		0.27
gMVP		0.54
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs35702888; hg19: chr17-56348208;