3-155084189-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007289.4(MME):c.22A>G(p.Met8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,613,950 control chromosomes in the GnomAD database, including 525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 33 hom., cov: 33)

Exomes 𝑓: 0.024 ( 492 hom. )

Consequence

MME
NM_007289.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.55

Variant links:

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]

MME links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007651925).

BP6

Variant 3-155084189-A-G is Benign according to our data. Variant chr3-155084189-A-G is described in ClinVar as [Benign]. Clinvar id is 1221640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-155084189-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0166 (2525/152306) while in subpopulation NFE AF= 0.0266 (1810/68028). AF 95% confidence interval is 0.0256. There are 33 homozygotes in gnomad4. There are 1190 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MME	NM_007289.4 link	c.22A>G	p.Met8Val	missense_variant	Exon 2 of 23	ENST00000360490.7	NP_009220.2	P08473

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7 link	c.22A>G	p.Met8Val	missense_variant	Exon 2 of 23	1	NM_007289.4	ENSP00000353679.2		P08473

Frequencies

GnomAD3 genomes

AF:

0.0166

AC:

2525

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0187

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0266

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0164

AC:

4119

AN:

251436

Hom.:

AF XY:

0.0171

AC XY:

2324

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00406

Gnomad AMR exome

AF:

0.0100

Gnomad ASJ exome

AF:

0.00218

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.0218

Gnomad NFE exome

AF:

0.0244

Gnomad OTH exome

AF:

0.0210

GnomAD4 exome

AF:

0.0237

AC:

34696

AN:

1461644

Hom.:

492

Cov.:

AF XY:

0.0235

AC XY:

17116

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00382

Gnomad4 AMR exome

AF:

0.0106

Gnomad4 ASJ exome

AF:

0.00187

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.0214

Gnomad4 NFE exome

AF:

0.0275

Gnomad4 OTH exome

AF:

0.0214

GnomAD4 genome

AF:

0.0166

AC:

2525

AN:

152306

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1190

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00493

Gnomad4 AMR

AF:

0.0142

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0112

Gnomad4 FIN

AF:

0.0187

Gnomad4 NFE

AF:

0.0266

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0221

Hom.:

Bravo

AF:

0.0156

TwinsUK

AF:

0.0245

AC:

ALSPAC

AF:

0.0278

AC:

107

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.0276

AC:

237

ExAC

AF:

0.0164

AC:

1990

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0250

EpiControl

AF:

0.0259

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

MME-related disorder

Benign:1

May 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;T;T;T;.;T;T;T;T;.;T;.;T;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.93

.;D;.;D;D;.;.;.;.;D;D;.;D;D

MetaRNN

Benign

0.0077

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.0083

MutationAssessor

Benign

0.90

L;.;L;.;.;.;L;L;L;.;.;.;.;L

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.88

N;.;N;N;.;D;N;N;N;N;N;D;N;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.019

D;.;D;D;.;D;D;D;D;D;T;.;T;.

Sift4G

Benign

0.54

T;D;T;T;D;D;T;T;T;T;D;.;T;T

Polyphen

0.52

P;.;P;.;.;.;P;P;P;.;.;.;.;P

Vest4

0.72

MPC

0.12

ClinPred

0.0068

GERP RS

5.3

Varity_R

0.33

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over