rs2016848

Variant names:

• chr3-155140896-G-A
• rs2016848
• NM_007289.4:c.957+604G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-155140896-G-A
• chr3-155140896-G-C
• chr3-155140896-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007289.4(MME):​c.957+604G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 151,706 control chromosomes in the GnomAD database, including 11,777 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (11777 hom., cov: 32)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• Publications: 11 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: 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

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.957+604G>A		intron	N/A	NP_009220.2	P08473
	MME	NM_000902.5		c.957+604G>A		intron	N/A	NP_000893.2	P08473
	MME	NM_001354642.2		c.957+604G>A		intron	N/A	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.957+604G>A		intron	N/A	ENSP00000353679.2	P08473
	MME	ENST00000615825.2	TSL:1	c.957+604G>A		intron	N/A	ENSP00000478173.2	A0A7I2U302
	MME	ENST00000460393.6	TSL:1	c.957+604G>A		intron	N/A	ENSP00000418525.1	P08473

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59227 AN: 151592 Hom.: 11760 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.399

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.391 AC: 59279 AN: 151706 Hom.: 11777 Cov.: 32 AF XY: 0.394 AC XY: 29223 AN XY: 74096

African (AFR) AF: 0.360 AC: 14896 AN: 41412

American (AMR) AF: 0.471 AC: 7184 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1207 AN: 3466

East Asian (EAS) AF: 0.467 AC: 2387 AN: 5112

South Asian (SAS) AF: 0.557 AC: 2686 AN: 4822

European-Finnish (FIN) AF: 0.356 AC: 3729 AN: 10482

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 25962 AN: 67862

Other (OTH) AF: 0.398 AC: 840 AN: 2110

Alfa AF: 0.389 Hom.: 11216

Bravo AF: 0.396

Asia WGS AF: 0.491 AC: 1706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.57
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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: rs2016848; hg19: chr3-154858685;