rs6797911

Positions:

• chr3-155144601-T-A
• chr3-155144601-T-C
• chr3-155144601-T-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.1416+144T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 631,642 control chromosomes in the GnomAD database, including 52,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (10713 hom., cov: 32)
  • Exomes 𝑓: 0.41 (41408 hom.)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.607

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-155144601-T-A is Benign according to our data. Variant chr3-155144601-T-A is described in ClinVar as [Benign]. Clinvar id is 1264196.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MME	NM_007289.4	c.1416+144T>A		intron_variant		ENST00000360490.7	NP_009220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7	c.1416+144T>A		intron_variant		1	NM_007289.4	ENSP00000353679.2

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55680 AN: 151664 Hom.: 10698 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.388

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.382

GnomAD4 exome AF: 0.408 AC: 195957 AN: 479860 Hom.: 41408 AF XY: 0.418 AC XY: 107144 AN XY: 256288

Gnomad4 AFR exome AF: 0.272

Gnomad4 AMR exome AF: 0.492

Gnomad4 ASJ exome AF: 0.361

Gnomad4 EAS exome AF: 0.470

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.398

GnomAD4 genome AF: 0.367 AC: 55721 AN: 151782 Hom.: 10713 Cov.: 32 AF XY: 0.372 AC XY: 27602 AN XY: 74164

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.381

Alfa AF: 0.377 Hom.: 1347

Bravo AF: 0.368

Asia WGS AF: 0.492 AC: 1706 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

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.62

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: rs6797911; hg19: chr3-154862390;