rs119469012

chr17-58272825-A-Cchr17-58272825-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_000250.2(MPO):c.1715T>G(p.Leu572Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPO NM_000250.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.32

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

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978
• PP5: Variant 17-58272825-A-C is Pathogenic according to our data. Variant chr17-58272825-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 3631.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-58272825-A-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPO	NM_000250.2	c.1715T>G	p.Leu572Trp	missense_variant	10/12	ENST00000225275.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPO	ENST00000225275.4	c.1715T>G	p.Leu572Trp	missense_variant	10/12	1	NM_000250.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Myeloperoxidase deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2004

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
Cadd	Pathogenic	28
Dann	Benign	0.96
DEOGEN2	Pathogenic	0.83	D;T
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;T
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Uncertain	0.54	D
MutationAssessor	Pathogenic	3.5	M;.
MutationTaster	Benign	1.0	A;A
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.0	D;.
REVEL	Pathogenic	0.76
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;.
Polyphen		1.0	D;.
Vest4		0.94
MutPred		0.91		Loss of stability (P = 0.0143);.;
MVP		0.98
MPC		1.5
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.97
gMVP		0.91

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: rs119469012; hg19: chr17-56350186;