NM_007289.4:c.1609A>C

Variant names:

• chr3-155160397-A-C
• rs2108350900
• NM_007289.4:c.1609A>C

Variant summary

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

The NM_007289.4(MME):​c.1609A>C​(p.Ser537Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MME NM_007289.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.82
• 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-AS1 (HGNC:40376): (MME antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MME	NM_007289.4	MANE Select	c.1609A>C	p.Ser537Arg	missense	Exon 17 of 23	NP_009220.2	P08473
	MME	NM_000902.5		c.1609A>C	p.Ser537Arg	missense	Exon 17 of 23	NP_000893.2	P08473
	MME	NM_001354642.2		c.1609A>C	p.Ser537Arg	missense	Exon 17 of 23	NP_001341571.1	P08473

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MME	ENST00000360490.7	TSL:1 MANE Select	c.1609A>C	p.Ser537Arg	missense	Exon 17 of 23	ENSP00000353679.2	P08473
	MME	ENST00000615825.2	TSL:1	c.1699A>C	p.Ser567Arg	missense	Exon 18 of 24	ENSP00000478173.2	A0A7I2U302
	MME	ENST00000460393.6	TSL:1	c.1609A>C	p.Ser537Arg	missense	Exon 17 of 23	ENSP00000418525.1	P08473

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.068	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.58
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.025	D
Polyphen		0.76	P
Vest4		0.71
MutPred		0.60		Gain of MoRF binding (P = 0.0194)
MVP		0.90
MPC		0.17
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.70
gMVP		0.89
Mutation Taster		=50/50

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: rs2108350900; hg19: chr3-154878186; COSMIC: COSV100852427;