NM_000250.2:c.995C>G

Variant names:

• chr17-58278036-G-C
• NM_000250.2:c.995C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_000250.2(MPO):​c.995C>G​(p.Ala332Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 12/21 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. A332V) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPO NM_000250.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.13

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr17-58278036-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPO	NM_000250.2	c.995C>G	p.Ala332Gly	missense_variant	Exon 7 of 12	ENST00000225275.4	NP_000241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPO	ENST00000225275.4	c.995C>G	p.Ala332Gly	missense_variant	Exon 7 of 12	1	NM_000250.2	ENSP00000225275.3
MPO	ENST00000578493.2	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 7	3
MPO	ENST00000699291.1	n.281C>G		non_coding_transcript_exon_variant	Exon 2 of 6			ENSP00000514272.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.3	L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.11
Sift	Benign	0.42	T
Sift4G	Benign	0.43	T
Polyphen		0.12	B
Vest4		0.53
MutPred		0.65		Loss of stability (P = 0.0545);
MVP		0.86
MPC		0.41
ClinPred		0.73	D
GERP RS		4.3
Varity_R		0.70
gMVP		0.65

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: chr17-56355397;