3-155109998-C-T

Position:

• chr3-155109998-C-T

Variant summary

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

The NM_007289.4(MME):​c.197-4996C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,130 control chromosomes in the GnomAD database, including 20,032 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 0.51 (20032 hom., cov: 33)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MME	NM_007289.4	c.197-4996C>T		intron_variant		ENST00000360490.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MME	ENST00000360490.7	c.197-4996C>T		intron_variant		1	NM_007289.4	P1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77605 AN: 152012 Hom.: 20017 Cov.: 33

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.510 AC: 77652 AN: 152130 Hom.: 20032 Cov.: 33 AF XY: 0.511 AC XY: 37973 AN XY: 74366

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.522

Alfa AF: 0.536 Hom.: 29694

Bravo AF: 0.513

Asia WGS AF: 0.542 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
DANN	Benign	0.81

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: rs1025192; hg19: chr3-154827787;