rs1436630

Positions:

• chr3-155112210-G-A
• chr3-155112210-G-T

Variant summary

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

The NM_007289.4(MME):​c.197-2784G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 151,994 control chromosomes in the GnomAD database, including 33,909 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 0.67 (33908 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MME	NM_007289.4	c.197-2784G>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.197-2784G>A		intron_variant		1	NM_007289.4	ENSP00000353679	P1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101253 AN: 151874 Hom.: 33884 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.687

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.667 AC: 101321 AN: 151992 Hom.: 33908 Cov.: 32 AF XY: 0.663 AC XY: 49262 AN XY: 74270

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.682

Alfa AF: 0.694 Hom.: 44269

Bravo AF: 0.672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.54

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: rs1436630; hg19: chr3-154829999;