rs200455903

Variant names:

• chr3-155160414-C-G
• rs200455903
• NM_007289.4:c.1626C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-155160414-C-G
• chr3-155160414-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_007289.4(MME):​c.1626C>G​(p.Val542Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000033 in 1,607,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: MME NM_007289.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.362
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 3-155160414-C-G is Benign according to our data. Variant chr3-155160414-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1568690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.362 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007289.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MME	NM_007289.4	MANE Select	c.1626C>G	p.Val542Val	synonymous	Exon 17 of 23	NP_009220.2	P08473
	MME	NM_000902.5		c.1626C>G	p.Val542Val	synonymous	Exon 17 of 23	NP_000893.2	P08473
	MME	NM_001354642.2		c.1626C>G	p.Val542Val	synonymous	Exon 17 of 23	NP_001341571.1	P08473

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MME	ENST00000360490.7	TSL:1 MANE Select	c.1626C>G	p.Val542Val	synonymous	Exon 17 of 23	ENSP00000353679.2	P08473
	MME	ENST00000615825.2	TSL:1	c.1716C>G	p.Val572Val	synonymous	Exon 18 of 24	ENSP00000478173.2	A0A7I2U302
	MME	ENST00000460393.6	TSL:1	c.1626C>G	p.Val542Val	synonymous	Exon 17 of 23	ENSP00000418525.1	P08473

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152018 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000558 AC: 14 AN: 251030 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000206 AC: 30 AN: 1455628 Hom.: 0 Cov.: 28 AF XY: 0.0000207 AC XY: 15 AN XY: 724560

African (AFR) AF: 0.00 AC: 0 AN: 33308

American (AMR) AF: 0.000336 AC: 15 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5720

European-Non Finnish (NFE) AF: 0.00000994 AC: 11 AN: 1106708

Other (OTH) AF: 0.0000333 AC: 2 AN: 60142

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152018 Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19 AN XY: 74244

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00144 AC: 22 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67926

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.000117

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.5
DANN	Benign	0.86
PhyloP100		0.36

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: rs200455903; hg19: chr3-154878203;