rs149905705

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong

The NM_007289.4(MME):c.1342C>T(p.Arg448*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000713 in 1,612,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

MME
NM_007289.4 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:8

Conservation

PhyloP100: 4.13

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease axonal type 2T
Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
MME-related autosomal dominant Charcot Marie Tooth disease type 2
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
spinocerebellar ataxia 43
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
Charcot-Marie-Tooth disease type 2T
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital membranous nephropathy due to maternal anti-neutral endopeptidase alloimmunization
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MME links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 16 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PP5

Variant 3-155144383-C-T is Pathogenic according to our data. Variant chr3-155144383-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 504903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007289.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MME	NM_007289.4	MANE Select	c.1342C>T	p.Arg448*	stop_gained	Exon 14 of 23	NP_009220.2	P08473
MME	NM_000902.5		c.1342C>T	p.Arg448*	stop_gained	Exon 14 of 23	NP_000893.2	P08473
MME	NM_001354642.2		c.1342C>T	p.Arg448*	stop_gained	Exon 14 of 23	NP_001341571.1	P08473

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MME	ENST00000360490.7	TSL:1 MANE Select	c.1342C>T	p.Arg448*	stop_gained	Exon 14 of 23	ENSP00000353679.2	P08473
MME	ENST00000615825.2	TSL:1	c.1342C>T	p.Arg448*	stop_gained	Exon 14 of 24	ENSP00000478173.2	A0A7I2U302
MME	ENST00000460393.6	TSL:1	c.1342C>T	p.Arg448*	stop_gained	Exon 14 of 23	ENSP00000418525.1	P08473

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000798

AC:

AN:

250696

AF XY:

0.0000812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000719

AC:

105

AN:

1460430

Hom.:

Cov.:

AF XY:

0.0000757

AC XY:

AN XY:

726598

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33418

American (AMR)

AF:

0.000336

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39590

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000765

AC:

AN:

1110956

Other (OTH)

AF:

0.0000497

AC:

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000658

AC:

AN:

151954

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.0000725

AC:

AN:

41364

American (AMR)

AF:

0.0000657

AC:

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68010

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Charcot-Marie-Tooth disease axonal type 2T (1)

Charcot-Marie-Tooth disease axonal type 2T;C4310763:Spinocerebellar ataxia 43 (1)

Congenital membranous nephropathy due to maternal anti-neutral endopeptidase alloimmunization (1)

MME-related disorder (1)

Spinocerebellar ataxia 43 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.66

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.97

PhyloP100

4.1

Vest4

0.99

GERP RS

5.9

Mutation Taster

=0/200

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over