Variant 3-127722510-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_007283.7(MGLL):c.319G>A(p.Val107Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,614,212 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000083 ( 1 hom. )

Consequence

MGLL
NM_007283.7 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.639

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012885779).

BP6

Variant 3-127722510-C-T is Benign according to our data. Variant chr3-127722510-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3035437.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGLL	NM_007283.7 link	c.319G>A	p.Val107Ile	missense_variant	4/8	ENST00000265052.10	NP_009214.1	Q99685A0A0C4DFN3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10 link	c.319G>A	p.Val107Ile	missense_variant	4/8	1	NM_007283.7	ENSP00000265052.5		A0A0C4DFN3

Frequencies

GnomAD3 genomes

AF:

0.000532

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000220

AC:

AN:

249584

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.00239

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000828

AC:

121

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000525

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0229

Hom.:

2353

Bravo

AF:

0.000684

ESP6500AA

AF:

0.00121

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000231

AC:

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

Jul 06, 2022

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

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.011

DANN

Benign

0.97

DEOGEN2

Benign

0.062

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

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.81

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

M_CAP

Benign

0.017

MetaRNN

Benign

0.013

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

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.94

.;.;L;L;.;.;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.63

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

REVEL

Benign

0.073

Sift

Benign

0.26

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

Sift4G

Benign

0.38

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

Polyphen

0.0030

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

Vest4

0.12

MVP

0.32

MPC

0.36

ClinPred

0.027

GERP RS

1.4

Varity_R

0.047

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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