3-155084178-C-T

Variant names:

• chr3-155084178-C-T
• NM_007289.4:c.11C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_007289.4(MME):​c.11C>T​(p.Ser4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MME NM_007289.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

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 4 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity NEP_HUMAN
• 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.11C>T	p.Ser4Leu	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.11C>T	p.Ser4Leu	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	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.63	D;T;D;T;.;T;D;D;D;.;T;.;T;D
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.97	.;D;.;D;D;.;.;.;.;D;D;.;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.60	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Benign	1.4	L;.;L;.;.;.;L;L;L;.;.;.;.;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.7	D;.;D;D;.;D;D;D;D;D;D;D;D;.
REVEL	Uncertain	0.50
Sift	Pathogenic	0.0	D;.;D;D;.;D;D;D;D;D;D;.;D;.
Sift4G	Uncertain	0.016	D;D;D;D;D;D;D;D;D;D;D;.;D;D
Polyphen		1.0	D;.;D;.;.;.;D;D;D;.;.;.;.;D
Vest4		0.58
MutPred		0.26		Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);Gain of stability (P = 0.0098);
MVP		0.97
MPC		0.26
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.35
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-154801967;