3-155117435-T-C

Position:

• chr3-155117435-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.654+449T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,100 control chromosomes in the GnomAD database, including 7,943 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 0.31 (7943 hom., cov: 32)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MME	NM_007289.4	c.654+449T>C		intron_variant		ENST00000360490.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MME	ENST00000360490.7	c.654+449T>C		intron_variant		1	NM_007289.4	P1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46724 AN: 151982 Hom.: 7940 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.307 AC: 46738 AN: 152100 Hom.: 7943 Cov.: 32 AF XY: 0.311 AC XY: 23154 AN XY: 74352

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.319

Alfa AF: 0.319 Hom.: 1027

Bravo AF: 0.306

Asia WGS AF: 0.407 AC: 1408 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3796268; hg19: chr3-154835224;