rs3736187

Variant names:

• chr3-155168489-T-C
• rs3736187
• NM_007289.4:c.1781-3T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007289.4(MME):​c.1781-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 1,609,340 control chromosomes in the GnomAD database, including 7,837 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1449 hom., cov: 32)
  • Exomes 𝑓: 0.083 (6388 hom.)
• Consequence: MME NM_007289.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001189
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.53
• Publications: 15 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-155168489-T-C is Benign according to our data. Variant chr3-155168489-T-C is described in ClinVar as Benign. ClinVar VariationId is 1243458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MME	NM_007289.4	c.1781-3T>C		splice_region_variant, intron_variant	Intron 18 of 22	ENST00000360490.7	NP_009220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7	c.1781-3T>C		splice_region_variant, intron_variant	Intron 18 of 22	1	NM_007289.4	ENSP00000353679.2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17895 AN: 151970 Hom.: 1438 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.0877

GnomAD2 exomes AF: 0.100 AC: 24887 AN: 248240 AF XY: 0.101

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.0473

Gnomad ASJ exome AF: 0.0341

Gnomad EAS exome AF: 0.175

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.0682

Gnomad OTH exome AF: 0.0798

GnomAD4 exome AF: 0.0829 AC: 120863 AN: 1457252 Hom.: 6388 Cov.: 31 AF XY: 0.0851 AC XY: 61741 AN XY: 725144

African (AFR) AF: 0.206 AC: 6882 AN: 33334

American (AMR) AF: 0.0508 AC: 2268 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.0332 AC: 867 AN: 26102

East Asian (EAS) AF: 0.200 AC: 7888 AN: 39444

South Asian (SAS) AF: 0.156 AC: 13431 AN: 86088

European-Finnish (FIN) AF: 0.155 AC: 8264 AN: 53304

Middle Eastern (MID) AF: 0.0486 AC: 280 AN: 5758

European-Non Finnish (NFE) AF: 0.0681 AC: 75519 AN: 1108430

Other (OTH) AF: 0.0908 AC: 5464 AN: 60184

GnomAD4 genome AF: 0.118 AC: 17931 AN: 152088 Hom.: 1449 Cov.: 32 AF XY: 0.123 AC XY: 9111 AN XY: 74322

African (AFR) AF: 0.204 AC: 8458 AN: 41488

American (AMR) AF: 0.0622 AC: 950 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3468

East Asian (EAS) AF: 0.171 AC: 882 AN: 5164

South Asian (SAS) AF: 0.165 AC: 794 AN: 4818

European-Finnish (FIN) AF: 0.168 AC: 1776 AN: 10560

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0697 AC: 4742 AN: 68004

Other (OTH) AF: 0.0887 AC: 187 AN: 2108

Alfa AF: 0.0866 Hom.: 552

Bravo AF: 0.112

Asia WGS AF: 0.164 AC: 568 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.77
PhyloP100		1.5
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0080
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: rs3736187; hg19: chr3-154886278; COSMIC: COSV107472327; COSMIC: COSV107472327;