rs10513469

Variant names:

• chr3-155117933-C-A
• rs10513469
• NM_007289.4:c.655-813C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-155117933-C-A
• chr3-155117933-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007289.4(MME):​c.655-813C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,944 control chromosomes in the GnomAD database, including 10,981 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (10981 hom., cov: 32)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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.655-813C>A		intron_variant	Intron 7 of 22	ENST00000360490.7	NP_009220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7	c.655-813C>A		intron_variant	Intron 7 of 22	1	NM_007289.4	ENSP00000353679.2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56199 AN: 151826 Hom.: 10968 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.391

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.370 AC: 56234 AN: 151944 Hom.: 10981 Cov.: 32 AF XY: 0.375 AC XY: 27869 AN XY: 74258

African (AFR) AF: 0.263 AC: 10924 AN: 41462

American (AMR) AF: 0.469 AC: 7163 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1259 AN: 3462

East Asian (EAS) AF: 0.469 AC: 2416 AN: 5154

South Asian (SAS) AF: 0.559 AC: 2691 AN: 4812

European-Finnish (FIN) AF: 0.385 AC: 4061 AN: 10550

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26493 AN: 67928

Other (OTH) AF: 0.388 AC: 820 AN: 2112

Alfa AF: 0.390 Hom.: 12170

Bravo AF: 0.369

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.4
DANN	Benign	0.71
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10513469; hg19: chr3-154835722;