rs6797911

Variant names:

• chr3-155144601-T-A
• rs6797911
• NM_007289.4:c.1416+144T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-155144601-T-A
• chr3-155144601-T-C
• chr3-155144601-T-G

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.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
• Publications: 5 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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease axonal type 2T

  Inheritance: SD, AR, AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• MME-related autosomal dominant Charcot Marie Tooth disease type 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spinocerebellar ataxia 43

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• Charcot-Marie-Tooth disease type 2T

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital membranous nephropathy due to maternal anti-neutral endopeptidase alloimmunization

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MME	NM_007289.4	c.1416+144T>A		intron_variant	Intron 14 of 22	ENST00000360490.7	NP_009220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7	c.1416+144T>A		intron_variant	Intron 14 of 22	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

African (AFR) AF: 0.272 AC: 3399 AN: 12502

American (AMR) AF: 0.492 AC: 9407 AN: 19110

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 5345 AN: 14808

East Asian (EAS) AF: 0.470 AC: 14418 AN: 30708

South Asian (SAS) AF: 0.569 AC: 26728 AN: 46942

European-Finnish (FIN) AF: 0.367 AC: 15921 AN: 43398

Middle Eastern (MID) AF: 0.429 AC: 918 AN: 2138

European-Non Finnish (NFE) AF: 0.385 AC: 109210 AN: 283626

Other (OTH) AF: 0.398 AC: 10611 AN: 26628

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

African (AFR) AF: 0.274 AC: 11361 AN: 41404

American (AMR) AF: 0.463 AC: 7061 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1208 AN: 3466

East Asian (EAS) AF: 0.471 AC: 2426 AN: 5148

South Asian (SAS) AF: 0.559 AC: 2695 AN: 4820

European-Finnish (FIN) AF: 0.356 AC: 3740 AN: 10496

Middle Eastern (MID) AF: 0.376 AC: 109 AN: 290

European-Non Finnish (NFE) AF: 0.383 AC: 26040 AN: 67902

Other (OTH) AF: 0.381 AC: 801 AN: 2104

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

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.62
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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: rs6797911; hg19: chr3-154862390;