3-155083576-T-C

Position:

• chr3-155083576-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007289.4(MME):​c.-10-582T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 156,450 control chromosomes in the GnomAD database, including 22,381 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 0.53 (21769 hom., cov: 32)
  • Exomes 𝑓: 0.51 (612 hom.)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MME	NM_007289.4	c.-10-582T>C		intron_variant		ENST00000360490.7	NP_009220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7	c.-10-582T>C		intron_variant		1	NM_007289.4	ENSP00000353679.2

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80076 AN: 151868 Hom.: 21764 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.509 AC: 2273 AN: 4464 Hom.: 612 Cov.: 0 AF XY: 0.518 AC XY: 1260 AN XY: 2434

Gnomad4 AFR exome AF: 0.409

Gnomad4 AMR exome AF: 0.539

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.719

Gnomad4 SAS exome AF: 0.711

Gnomad4 FIN exome AF: 0.591

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.457

GnomAD4 genome AF: 0.527 AC: 80109 AN: 151986 Hom.: 21769 Cov.: 32 AF XY: 0.538 AC XY: 40010 AN XY: 74318

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.555

Alfa AF: 0.532 Hom.: 28384

Bravo AF: 0.513

Asia WGS AF: 0.721 AC: 2508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.3
DANN	Benign	0.80

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: rs989692; hg19: chr3-154801365;