rs701109

Variant names:

• chr3-155180618-C-T
• rs701109
• NM_007289.4:c.*159C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MME	NM_007289.4	c.*159C>T		3_prime_UTR_variant	Exon 23 of 23	ENST00000360490.7	NP_009220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7	c.*159C>T		3_prime_UTR_variant	Exon 23 of 23	1	NM_007289.4	ENSP00000353679.2

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

African (AFR) AF: 0.579 AC: 8249 AN: 14258

American (AMR) AF: 0.251 AC: 7688 AN: 30588

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 6320 AN: 17682

East Asian (EAS) AF: 0.417 AC: 12849 AN: 30798

South Asian (SAS) AF: 0.398 AC: 23309 AN: 58604

European-Finnish (FIN) AF: 0.369 AC: 16971 AN: 45972

Middle Eastern (MID) AF: 0.333 AC: 1166 AN: 3502

European-Non Finnish (NFE) AF: 0.367 AC: 109294 AN: 298102

Other (OTH) AF: 0.379 AC: 10770 AN: 28390

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

African (AFR) AF: 0.578 AC: 23956 AN: 41446

American (AMR) AF: 0.292 AC: 4453 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3468

East Asian (EAS) AF: 0.376 AC: 1935 AN: 5150

South Asian (SAS) AF: 0.424 AC: 2044 AN: 4816

European-Finnish (FIN) AF: 0.381 AC: 4023 AN: 10572

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25035 AN: 67936

Other (OTH) AF: 0.382 AC: 806 AN: 2110

Alfa AF: 0.375 Hom.: 19095

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

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.59
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs701109; hg19: chr3-154898407;