rs3773885

Variant names:

• chr3-155141792-G-A
• rs3773885
• NM_007289.4:c.958-199G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007289.4(MME):​c.958-199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,810 control chromosomes in the GnomAD database, including 9,064 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (9064 hom., cov: 32)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0360
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-155141792-G-A is Benign according to our data. Variant chr3-155141792-G-A is described in ClinVar as Benign. ClinVar VariationId is 1226057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 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.958-199G>A		intron	N/A	NP_009220.2	P08473
	MME	NM_000902.5		c.958-199G>A		intron	N/A	NP_000893.2	P08473
	MME	NM_001354642.2		c.958-199G>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.958-199G>A		intron	N/A	ENSP00000353679.2	P08473
	MME	ENST00000615825.2	TSL:1	c.958-199G>A		intron	N/A	ENSP00000478173.2	A0A7I2U302
	MME	ENST00000460393.6	TSL:1	c.958-199G>A		intron	N/A	ENSP00000418525.1	P08473

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51188 AN: 151696 Hom.: 9055 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.337 AC: 51225 AN: 151810 Hom.: 9064 Cov.: 32 AF XY: 0.342 AC XY: 25365 AN XY: 74150

African (AFR) AF: 0.261 AC: 10795 AN: 41424

American (AMR) AF: 0.443 AC: 6754 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3468

East Asian (EAS) AF: 0.467 AC: 2412 AN: 5160

South Asian (SAS) AF: 0.484 AC: 2330 AN: 4816

European-Finnish (FIN) AF: 0.329 AC: 3456 AN: 10490

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23377 AN: 67894

Other (OTH) AF: 0.355 AC: 748 AN: 2106

Alfa AF: 0.351 Hom.: 1772

Bravo AF: 0.342

Asia WGS AF: 0.457 AC: 1583 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.5
DANN	Benign	0.25
PhyloP100		0.036
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: rs3773885; hg19: chr3-154859581;