Variant 3-127821802-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_007283.7(MGLL):c.47C>T(p.Ser16Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000797 in 1,614,118 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00076 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00080 ( 4 hom. )

Consequence

MGLL
NM_007283.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.22

Variant links:

Genes affected

MGLL (HGNC:17038): (monoglyceride lipase) This gene encodes a serine hydrolase of the AB hydrolase superfamily that catalyzes the conversion of monoacylglycerides to free fatty acids and glycerol. The encoded protein plays a critical role in several physiological processes including pain and nociperception through hydrolysis of the endocannabinoid 2-arachidonoylglycerol. Expression of this gene may play a role in cancer tumorigenesis and metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

MGLL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069710016).

BP6

Variant 3-127821802-G-A is Benign according to our data. Variant chr3-127821802-G-A is described in ClinVar as [Benign]. Clinvar id is 2672955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGLL	NM_007283.7 linkuse as main transcript	c.47C>T	p.Ser16Phe	missense_variant	2/8	ENST00000265052.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGLL	ENST00000265052.10 linkuse as main transcript	c.47C>T	p.Ser16Phe	missense_variant	2/8	1	NM_007283.7

Frequencies

GnomAD3 genomes

AF:

0.000756

AC:

115

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00137

AC:

343

AN:

249472

Hom.:

AF XY:

0.00125

AC XY:

169

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000556

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.000801

AC:

1171

AN:

1461822

Hom.:

Cov.:

AF XY:

0.000821

AC XY:

597

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.0221

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000314

Gnomad4 OTH exome

AF:

0.00288

GnomAD4 genome

AF:

0.000755

AC:

115

AN:

152296

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000914

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.000971

ESP6500AA

AF:

0.000267

AC:

ESP6500EA

AF:

0.00122

AC:

ExAC

AF:

0.000977

AC:

118

EpiCase

AF:

0.000545

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

MGLL: BP4, BS1, BS2 -

MGLL-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 03, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Uncertain

0.060

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.89

D;D;D;.;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.0070

T;T;T;T;T;T

MetaSVM

Benign

-0.57

MutationTaster

Benign

0.75

D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.5

N;D;D;D;.;D

REVEL

Benign

0.22

Sift

Uncertain

0.0040

D;D;D;D;.;D

Sift4G

Uncertain

0.015

D;D;D;D;.;.

Polyphen

0.67

.;.;P;P;.;.

Vest4

0.51

MVP

0.26

MPC

1.4

ClinPred

0.068

GERP RS

4.2

Varity_R

0.17

gMVP

0.41

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

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