rs61760379

Variant names:

• chr3-155160096-C-T
• rs61760379
• NM_007289.4:c.1602-294C>T

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.1602-294C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 152,106 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.021 (65 hom., cov: 32)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.992
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-155160096-C-T is Benign according to our data. Variant chr3-155160096-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1207127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MME	NM_007289.4	MANE Select	c.1602-294C>T		intron	N/A	NP_009220.2
	MME	NM_000902.5		c.1602-294C>T		intron	N/A	NP_000893.2
	MME	NM_001354642.2		c.1602-294C>T		intron	N/A	NP_001341571.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MME	ENST00000360490.7	TSL:1 MANE Select	c.1602-294C>T		intron	N/A	ENSP00000353679.2
	MME	ENST00000615825.2	TSL:1	c.1692-294C>T		intron	N/A	ENSP00000478173.2
	MME	ENST00000460393.6	TSL:1	c.1602-294C>T		intron	N/A	ENSP00000418525.1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3166 AN: 151990 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.00862

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0644

Gnomad FIN AF: 0.0268

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0157

Gnomad OTH AF: 0.0211

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

GnomAD4 genome AF: 0.0208 AC: 3167 AN: 152106 Hom.: 65 Cov.: 32 AF XY: 0.0229 AC XY: 1702 AN XY: 74336

African (AFR) AF: 0.00862 AC: 358 AN: 41548

American (AMR) AF: 0.0276 AC: 421 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3470

East Asian (EAS) AF: 0.112 AC: 580 AN: 5168

South Asian (SAS) AF: 0.0643 AC: 310 AN: 4824

European-Finnish (FIN) AF: 0.0268 AC: 284 AN: 10596

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.0157 AC: 1067 AN: 67932

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0164 Hom.: 2

Bravo AF: 0.0204

Asia WGS AF: 0.0590 AC: 203 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Likely 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	-0.82
CADD	Benign	9.0
DANN	Benign	0.50
PhyloP100		0.99
Mutation Taster		=100/0	polymorphism

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: rs61760379; hg19: chr3-154877885;