3-155083948-A-G

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.-10-210A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 530,314 control chromosomes in the GnomAD database, including 11,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3500 hom., cov: 32)
  • Exomes 𝑓: 0.20 (8256 hom.)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-155083948-A-G is Benign according to our data. Variant chr3-155083948-A-G is described in ClinVar as [Benign]. Clinvar id is 1258480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MME	NM_007289.4	c.-10-210A>G		intron_variant		ENST00000360490.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MME	ENST00000360490.7	c.-10-210A>G		intron_variant		1	NM_007289.4	P1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32407 AN: 152024 Hom.: 3495 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.203 AC: 76787 AN: 378172 Hom.: 8256 Cov.: 4 AF XY: 0.201 AC XY: 40501 AN XY: 201188

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.213 AC: 32420 AN: 152142 Hom.: 3500 Cov.: 32 AF XY: 0.211 AC XY: 15696 AN XY: 74384

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.224

Alfa AF: 0.214 Hom.: 718

Bravo AF: 0.212

Asia WGS AF: 0.165 AC: 573 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.3
Dann	Benign	0.77

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: rs3773905; hg19: chr3-154801737;