Variant 3-155168489-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007289.4(MME):c.1781-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 1,609,340 control chromosomes in the GnomAD database, including 7,837 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1449 hom., cov: 32)

Exomes 𝑓: 0.083 ( 6388 hom. )

Consequence

MME
NM_007289.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001189

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.53

Variant links:

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 links:

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

MME-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-155168489-T-C is Benign according to our data. Variant chr3-155168489-T-C is described in ClinVar as [Benign]. Clinvar id is 1243458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-155168489-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MME	NM_007289.4 linkuse as main transcript	c.1781-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000360490.7	NP_009220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MME	ENST00000360490.7 linkuse as main transcript	c.1781-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_007289.4	ENSP00000353679	P1
MME-AS1	ENST00000484721.2 linkuse as main transcript	n.215-9506A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17895

AN:

151970

Hom.:

1438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0623

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0697

Gnomad OTH

AF:

0.0877

GnomAD3 exomes

AF:

0.100

AC:

24887

AN:

248240

Hom.:

1634

AF XY:

0.101

AC XY:

13636

AN XY:

134590

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.0473

Gnomad ASJ exome

AF:

0.0341

Gnomad EAS exome

AF:

0.175

Gnomad SAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.0682

Gnomad OTH exome

AF:

0.0798

GnomAD4 exome

AF:

0.0829

AC:

120863

AN:

1457252

Hom.:

6388

Cov.:

AF XY:

0.0851

AC XY:

61741

AN XY:

725144

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.0508

Gnomad4 ASJ exome

AF:

0.0332

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.155

Gnomad4 NFE exome

AF:

0.0681

Gnomad4 OTH exome

AF:

0.0908

GnomAD4 genome

AF:

0.118

AC:

17931

AN:

152088

Hom.:

1449

Cov.:

AF XY:

0.123

AC XY:

9111

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.204

Gnomad4 AMR

AF:

0.0622

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.171

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.168

Gnomad4 NFE

AF:

0.0697

Gnomad4 OTH

AF:

0.0887

Alfa

AF:

0.0849

Hom.:

482

Bravo

AF:

0.112

Asia WGS

AF:

0.164

AC:

568

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.1

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over