Variant 3-155180338-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007289.4(MME):c.2154-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 1,589,878 control chromosomes in the GnomAD database, including 7,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.12 ( 1431 hom., cov: 32)

Exomes 𝑓: 0.084 ( 6407 hom. )

Consequence

MME
NM_007289.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.977

Variant links:

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 links:

MME-AS1 (HGNC:):

MME-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 3-155180338-A-G is Benign according to our data. Variant chr3-155180338-A-G is described in ClinVar as [Benign]. Clinvar id is 1261728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MME	NM_007289.4 linkuse as main transcript	c.2154-22A>G		intron_variant		ENST00000360490.7	NP_009220.2	P08473

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7 linkuse as main transcript	c.2154-22A>G		intron_variant		1	NM_007289.4	ENSP00000353679.2		P08473

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17841

AN:

152056

Hom.:

1422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0613

Gnomad ASJ

AF:

0.0360

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0703

Gnomad OTH

AF:

0.0851

GnomAD3 exomes

AF:

0.101

AC:

25237

AN:

250280

Hom.:

1683

AF XY:

0.102

AC XY:

13816

AN XY:

135502

show subpopulations

Gnomad AFR exome

AF:

0.207

Gnomad AMR exome

AF:

0.0465

Gnomad ASJ exome

AF:

0.0369

Gnomad EAS exome

AF:

0.179

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.0685

Gnomad OTH exome

AF:

0.0809

GnomAD4 exome

AF:

0.0838

AC:

120447

AN:

1437704

Hom.:

6407

Cov.:

AF XY:

0.0860

AC XY:

61669

AN XY:

716894

show subpopulations

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.0500

Gnomad4 ASJ exome

AF:

0.0367

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.156

Gnomad4 NFE exome

AF:

0.0689

Gnomad4 OTH exome

AF:

0.0907

GnomAD4 genome

AF:

0.117

AC:

17872

AN:

152174

Hom.:

1431

Cov.:

AF XY:

0.122

AC XY:

9077

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.0612

Gnomad4 ASJ

AF:

0.0360

Gnomad4 EAS

AF:

0.174

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.0703

Gnomad4 OTH

AF:

0.0842

Alfa

AF:

0.0753

Hom.:

208

Bravo

AF:

0.111

Asia WGS

AF:

0.163

AC:

564

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.61

BranchPoint Hunter

3.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over