rs701109

Positions:

• chr3-155180618-C-T

Variant summary

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

The NM_007289.4(MME):​c.*159C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 679,846 control chromosomes in the GnomAD database, including 51,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14301 hom., cov: 31)
  • Exomes 𝑓: 0.37 (37524 hom.)
• Consequence: MME NM_007289.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.102

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]

MME-AS1 (HGNC:40376): (MME antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-155180618-C-T is Benign according to our data. Variant chr3-155180618-C-T is described in ClinVar as [Benign]. Clinvar id is 1282217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MME	NM_007289.4	c.*159C>T		3_prime_UTR_variant	23/23	ENST00000360490.7	NP_009220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7	c.*159C>T		3_prime_UTR_variant	23/23	1	NM_007289.4	ENSP00000353679	P1
MME-AS1	ENST00000484721.2	n.214+2454G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63959 AN: 151830 Hom.: 14275 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.385

GnomAD4 exome AF: 0.372 AC: 196616 AN: 527896 Hom.: 37524 Cov.: 5 AF XY: 0.374 AC XY: 105983 AN XY: 283736

Gnomad4 AFR exome AF: 0.579

Gnomad4 AMR exome AF: 0.251

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.398

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.379

GnomAD4 genome AF: 0.421 AC: 64022 AN: 151950 Hom.: 14301 Cov.: 31 AF XY: 0.419 AC XY: 31118 AN XY: 74260

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.382

Alfa AF: 0.369 Hom.: 14610

Bravo AF: 0.421

Asia WGS AF: 0.380 AC: 1320 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 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.59

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: rs701109; hg19: chr3-154898407;