rs35450782

Variant names:

• chr3-155160369-GA-G
• rs35450782
• NM_007289.4:c.1602-20delA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_007289.4(MME):​c.1602-20delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,559,770 control chromosomes in the GnomAD database, including 58,122 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5208 hom., cov: 22)
  • Exomes 𝑓: 0.27 (52914 hom.)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.613
• 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-AS1 (HGNC:40376): (MME antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 3-155160369-GA-G is Benign according to our data. Variant chr3-155160369-GA-G is described in ClinVar as Benign. ClinVar VariationId is 1240795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 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.1602-20delA		intron	N/A	NP_009220.2	P08473
	MME	NM_000902.5		c.1602-20delA		intron	N/A	NP_000893.2	P08473
	MME	NM_001354642.2		c.1602-20delA		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.1602-20delA		intron	N/A	ENSP00000353679.2	P08473
	MME	ENST00000615825.2	TSL:1	c.1692-20delA		intron	N/A	ENSP00000478173.2	A0A7I2U302
	MME	ENST00000460393.6	TSL:1	c.1602-20delA		intron	N/A	ENSP00000418525.1	P08473

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39008 AN: 151780 Hom.: 5203 Cov.: 22

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.261

GnomAD2 exomes AF: 0.229 AC: 57370 AN: 250728 AF XY: 0.232

Gnomad AFR exome AF: 0.281

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.297

Gnomad EAS exome AF: 0.0773

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.267 AC: 375999 AN: 1407872 Hom.: 52914 Cov.: 12 AF XY: 0.265 AC XY: 186658 AN XY: 703834

African (AFR) AF: 0.275 AC: 8890 AN: 32288

American (AMR) AF: 0.147 AC: 6564 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 7658 AN: 25684

East Asian (EAS) AF: 0.0846 AC: 3329 AN: 39366

South Asian (SAS) AF: 0.182 AC: 15493 AN: 85202

European-Finnish (FIN) AF: 0.193 AC: 10273 AN: 53290

Middle Eastern (MID) AF: 0.261 AC: 1467 AN: 5618

European-Non Finnish (NFE) AF: 0.289 AC: 307055 AN: 1063292

Other (OTH) AF: 0.261 AC: 15270 AN: 58494

GnomAD4 genome AF: 0.257 AC: 39026 AN: 151898 Hom.: 5208 Cov.: 22 AF XY: 0.249 AC XY: 18471 AN XY: 74244

African (AFR) AF: 0.277 AC: 11493 AN: 41448

American (AMR) AF: 0.195 AC: 2972 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3468

East Asian (EAS) AF: 0.0780 AC: 404 AN: 5178

South Asian (SAS) AF: 0.189 AC: 911 AN: 4824

European-Finnish (FIN) AF: 0.184 AC: 1950 AN: 10574

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.283 AC: 19220 AN: 67844

Other (OTH) AF: 0.259 AC: 546 AN: 2106

Alfa AF: 0.184 Hom.: 533

Bravo AF: 0.260

Asia WGS AF: 0.148 AC: 516 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs35450782; hg19: chr3-154878158;