rs200770339

Variant names:

• chr3-155160717-TTTTTA-T
• rs200770339
• NM_007289.4:c.1660+278_1660+282delTATTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_007289.4(MME):​c.1660+278_1660+282delTATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 152,222 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0058 (4 hom., cov: 32)
• Consequence: MME NM_007289.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.61

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 -10 ACMG points.

• BP6: Variant 3-155160717-TTTTTA-T is Benign according to our data. Variant chr3-155160717-TTTTTA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1194720.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00583 (888/152222) while in subpopulation AFR AF= 0.0204 (846/41562). AF 95% confidence interval is 0.0192. There are 4 homozygotes in gnomad4. There are 443 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MME	NM_007289.4	c.1660+278_1660+282delTATTT		intron_variant	Intron 17 of 22	ENST00000360490.7	NP_009220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7	c.1660+270_1660+274delTTTTA		intron_variant	Intron 17 of 22	1	NM_007289.4	ENSP00000353679.2

Frequencies

GnomAD3 genomes AF: 0.00579 AC: 881 AN: 152104 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00575

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

GnomAD4 genome AF: 0.00583 AC: 888 AN: 152222 Hom.: 4 Cov.: 32 AF XY: 0.00595 AC XY: 443 AN XY: 74424

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00577 Hom.: 1

Bravo AF: 0.00657

Asia WGS AF: 0.00203 AC: 7 AN: 3454

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 24, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200770339; hg19: chr3-154878506;