rs61760379

Positions:

• chr3-155160096-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MME	NM_007289.4	c.1602-294C>T		intron_variant		ENST00000360490.7	NP_009220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7	c.1602-294C>T		intron_variant		1	NM_007289.4	ENSP00000353679.2

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

Gnomad4 AFR AF: 0.00862

Gnomad4 AMR AF: 0.0276

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0643

Gnomad4 FIN AF: 0.0268

Gnomad4 NFE AF: 0.0157

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0164 Hom.: 2

Bravo AF: 0.0204

Asia WGS AF: 0.0590 AC: 203 AN: 3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

This variant is associated with the following publications: (PMID: 15860464) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs61760379; hg19: chr3-154877885;