3-155078571-C-T

Position:

• chr3-155078571-C-T

Variant summary

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

The NM_001354642.2(MME):​c.-10-5587C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.984 in 152,166 control chromosomes in the GnomAD database, including 73,698 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 0.98 (73698 hom., cov: 30)
• Consequence: MME NM_001354642.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

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 (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MME	NM_001354642.2	c.-10-5587C>T		intron_variant			NP_001341571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000492661.5	c.-10-5587C>T		intron_variant		2		ENSP00000420389.1

Frequencies

GnomAD3 genomes AF: 0.984 AC: 149632 AN: 152048 Hom.: 73639 Cov.: 30

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.991

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.989

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

GnomAD4 genome AF: 0.984 AC: 149750 AN: 152166 Hom.: 73698 Cov.: 30 AF XY: 0.985 AC XY: 73252 AN XY: 74368

Gnomad4 AFR AF: 0.995

Gnomad4 AMR AF: 0.991

Gnomad4 ASJ AF: 0.995

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.973

Gnomad4 OTH AF: 0.990

Alfa AF: 0.977 Hom.: 89777

Bravo AF: 0.985

Asia WGS AF: 0.998 AC: 3471 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	1.8
DANN	Benign	0.74

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: rs1836914; hg19: chr3-154796360;