Variant 3-127692221-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 ENST00000265052.10(MGLL):c.919G>A(p.Ala307Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,613,696 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0035 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0049 ( 38 hom. )

Consequence

MGLL
ENST00000265052.10 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.248

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=0.0033406615).

BP6

Variant 3-127692221-C-T is Benign according to our data. Variant chr3-127692221-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3039230.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGLL	NM_007283.7 linkuse as main transcript	c.919G>A	p.Ala307Thr	missense_variant	8/8	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10 linkuse as main transcript	c.919G>A	p.Ala307Thr	missense_variant	8/8	1	NM_007283.7	ENSP00000265052

Frequencies

GnomAD3 genomes

AF:

0.00349

AC:

530

AN:

151762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000847

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.0164

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00431

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00352

AC:

879

AN:

249570

Hom.:

AF XY:

0.00338

AC XY:

458

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.00461

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.00486

AC:

7102

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

3391

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.0135

Gnomad4 NFE exome

AF:

0.00549

Gnomad4 OTH exome

AF:

0.00311

GnomAD4 genome

AF:

0.00349

AC:

530

AN:

151880

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

303

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.000845

Gnomad4 AMR

AF:

0.00138

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.0164

Gnomad4 NFE

AF:

0.00431

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00412

Hom.:

Bravo

AF:

0.00257

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.00437

AC:

ExAC

AF:

0.00320

AC:

387

EpiCase

AF:

0.00371

EpiControl

AF:

0.00320

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MGLL-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 12, 2019

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

0.071

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

4.1

DANN

Benign

0.86

DEOGEN2

Benign

0.084

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.70

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

MetaRNN

Benign

0.0033

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

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

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.34

N;N;N;N;N;N;N

REVEL

Benign

0.018

Sift

Benign

0.40

T;T;T;T;D;T;T

Sift4G

Benign

0.26

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

Polyphen

0.0

.;.;B;B;.;B;.

Vest4

0.050

MVP

0.048

MPC

0.43

ClinPred

0.00067

GERP RS

1.1

Varity_R

0.024

gMVP

0.26

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