11-59211211-G-T

Position:

• chr11-59211211-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001039396.2(MPEG1):​c.1655C>A​(p.Pro552Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P552L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPEG1 NM_001039396.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72

Genes affected

MPEG1 (HGNC:29619): (macrophage expressed 1) Involved in defense response to Gram-negative bacterium and defense response to Gram-positive bacterium. Located in cytoplasmic vesicle. Implicated in primary immunodeficiency disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPEG1	NM_001039396.2	c.1655C>A	p.Pro552Gln	missense_variant	1/1	ENST00000361050.4	NP_001034485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPEG1	ENST00000361050.4	c.1655C>A	p.Pro552Gln	missense_variant	1/1		NM_001039396.2	ENSP00000354335	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2023

The c.1655C>A (p.P552Q) alteration is located in exon 1 (coding exon 1) of the MPEG1 gene. This alteration results from a C to A substitution at nucleotide position 1655, causing the proline (P) at amino acid position 552 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0040	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.081
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.13
Sift	Benign	0.093	T
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.62
MutPred		0.22		Gain of solvent accessibility (P = 0.0365);
MVP		0.28
MPC		0.40
ClinPred		0.84	D
GERP RS		4.7
Varity_R		0.14
gMVP		0.40

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: chr11-58978684;