3-155084043-G-A

Position:

• chr3-155084043-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000360490.7(MME):​c.-10-115G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,010,870 control chromosomes in the GnomAD database, including 22,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2578 hom., cov: 33)
  • Exomes 𝑓: 0.20 (20318 hom.)
• Consequence: MME ENST00000360490.7 intron
• Scores: Splicing: ADA: 0.00003835
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.28

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-155084043-G-A is Benign according to our data. Variant chr3-155084043-G-A is described in ClinVar as [Benign]. Clinvar id is 1279010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MME	NM_007289.4	c.-10-115G>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.-10-115G>A		intron_variant		1	NM_007289.4	ENSP00000353679	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25258 AN: 152042 Hom.: 2578 Cov.: 33

Gnomad AFR AF: 0.0712

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0354

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.204 AC: 175358 AN: 858710 Hom.: 20318 Cov.: 11 AF XY: 0.199 AC XY: 88304 AN XY: 442930

Gnomad4 AFR exome AF: 0.0634

Gnomad4 AMR exome AF: 0.0985

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.0449

Gnomad4 SAS exome AF: 0.0610

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.166 AC: 25256 AN: 152160 Hom.: 2578 Cov.: 33 AF XY: 0.161 AC XY: 11990 AN XY: 74402

Gnomad4 AFR AF: 0.0709

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0353

Gnomad4 SAS AF: 0.0550

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.160

Alfa AF: 0.215 Hom.: 756

Bravo AF: 0.155

Asia WGS AF: 0.0560 AC: 197 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.92
CADD	Benign	0.42
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
dbscSNV1_RF	Benign	0.082
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: rs56208271; hg19: chr3-154801832;