rs142421146

Variant names:

• chr3-155084209-C-A
• rs142421146
• NM_007289.4:c.42C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-155084209-C-A
• chr3-155084209-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007289.4(MME):​c.42C>A​(p.Asn14Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N14N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MME NM_007289.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 0 publications found

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: SD, AR, AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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, Labcorp Genetics (formerly Invitae), Orphanet
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18904558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MME	NM_007289.4	c.42C>A	p.Asn14Lys	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.42C>A	p.Asn14Lys	missense_variant	Exon 2 of 23	1	NM_007289.4	ENSP00000353679.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;T;T;T;.;T;T;T;T;.;T;.;T;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.058
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.86	.;D;.;D;D;.;.;.;.;D;D;.;D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.2	M;.;M;.;.;.;M;M;M;.;.;.;.;M
PhyloP100		1.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.12	N;.;N;N;.;N;N;N;N;N;N;D;N;.
REVEL	Benign	0.18
Sift	Benign	0.18	T;.;T;T;.;D;T;T;T;T;T;.;T;.
Sift4G	Benign	1.0	T;D;T;T;D;D;T;T;T;T;T;.;T;T
Polyphen		0.017	B;.;B;.;.;.;B;B;B;.;.;.;.;B
Vest4		0.68
MutPred		0.26		Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);Gain of methylation at N14 (P = 0.0042);
MVP		0.88
MPC		0.078
ClinPred		0.60	D
GERP RS		4.4
PromoterAI		-0.040	Neutral
Varity_R		0.055
gMVP		0.33
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs142421146; hg19: chr3-154801998;