rs3773885

Positions:

• chr3-155141792-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007289.4(MME):​c.958-199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,810 control chromosomes in the GnomAD database, including 9,064 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (9064 hom., cov: 32)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0360

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-155141792-G-A is Benign according to our data. Variant chr3-155141792-G-A is described in ClinVar as [Benign]. Clinvar id is 1226057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MME	NM_007289.4	c.958-199G>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.958-199G>A		intron_variant		1	NM_007289.4	ENSP00000353679.2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51188 AN: 151696 Hom.: 9055 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.337 AC: 51225 AN: 151810 Hom.: 9064 Cov.: 32 AF XY: 0.342 AC XY: 25365 AN XY: 74150

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.355

Alfa AF: 0.353 Hom.: 1737

Bravo AF: 0.342

Asia WGS AF: 0.457 AC: 1583 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.5
DANN	Benign	0.25

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: rs3773885; hg19: chr3-154859581;