3-155084190-T-G

Variant names:

• chr3-155084190-T-G
• NM_007289.4:c.23T>G

Variant summary

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

The NM_007289.4(MME):​c.23T>G​(p.Met8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M8V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MME NM_007289.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98

Genes affected

MME (HGNC:7154): (membrane metalloendopeptidase) The protein encoded by this gene is a type II transmembrane glycoprotein and a common acute lymphocytic leukemia antigen that is an important cell surface marker in the diagnosis of human acute lymphocytic leukemia (ALL). The encoded protein is present on leukemic cells of pre-B phenotype, which represent 85% of cases of ALL. This protein is not restricted to leukemic cells, however, and is found on a variety of normal tissues. The protein is a neutral endopeptidase that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin. [provided by RefSeq, Aug 2017]

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 rank	MANE	Protein	UniProt
MME	NM_007289.4	c.23T>G	p.Met8Arg	missense_variant	Exon 2 of 23	ENST00000360490.7	NP_009220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7	c.23T>G	p.Met8Arg	missense_variant	Exon 2 of 23	1	NM_007289.4	ENSP00000353679.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461836 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Dec 20, 2018

Kariminejad - Najmabadi Pathology & Genetics Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PM2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T;T;T;T;.;T;T;T;T;.;T;.;T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.92	.;D;.;D;D;.;.;.;.;D;D;.;D;D
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Benign	1.2	L;.;L;.;.;.;L;L;L;.;.;.;.;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.1	N;.;N;N;.;D;N;N;N;N;N;D;D;.
REVEL	Uncertain	0.64
Sift	Uncertain	0.0030	D;.;D;D;.;D;D;D;D;D;D;.;D;.
Sift4G	Benign	0.10	T;D;T;D;D;D;T;T;T;D;D;.;D;T
Polyphen		0.97	D;.;D;.;.;.;D;D;D;.;.;.;.;D
Vest4		0.90
MutPred		0.24		Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);
MVP		0.98
MPC		0.36
ClinPred		0.85	D
GERP RS		5.3
Varity_R		0.78
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-154801979;