Variant chr3-127695133-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_007283.7(MGLL):c.658G>A(p.Gly220Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00103 in 1,614,136 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 13 hom. )

Consequence

MGLL
NM_007283.7 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077992976).

BP6

Variant 3-127695133-C-T is Benign according to our data. Variant chr3-127695133-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042845.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7 link	c.658G>A	p.Gly220Ser	missense_variant	Exon 7 of 8	ENST00000265052.10	NP_009214.1	Q99685A0A0C4DFN3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10 link	c.658G>A	p.Gly220Ser	missense_variant	Exon 7 of 8	1	NM_007283.7	ENSP00000265052.5		A0A0C4DFN3

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

223

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00621

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0125

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00311

AC:

777

AN:

249442

Hom.:

AF XY:

0.00272

AC XY:

368

AN XY:

135372

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0114

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.0124

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00311

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.000988

AC:

1444

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000939

AC XY:

683

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.0106

Gnomad4 SAS exome

AF:

0.00153

Gnomad4 FIN exome

AF:

0.00326

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00147

AC:

224

AN:

152290

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0125

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00301

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000872

Hom.:

Bravo

AF:

0.00201

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000357

AC:

ExAC

AF:

0.00251

AC:

304

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MGLL-related disorder

Benign:1

Mar 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

0.32

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

.;.;T;T;.;.;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D;D;.;D;D;D

MetaRNN

Benign

0.0078

T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.5

.;.;M;M;.;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.1

N;N;N;N;N;.;N

REVEL

Uncertain

0.36

Sift

Benign

0.42

T;T;T;T;T;.;T

Sift4G

Benign

0.17

T;T;T;T;T;.;T

Polyphen

0.86, 0.95

.;.;P;P;P;.;.

Vest4

0.50

MVP

0.86

MPC

0.60

ClinPred

0.025

GERP RS

5.0

Varity_R

0.49

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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