Genetic Variant MGLL:p.Asp202Tyr (chr3-127695187-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007283.7(MGLL):c.604G>T(p.Asp202Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D202N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

MGLL
NM_007283.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.14

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7 link	c.604G>T	p.Asp202Tyr	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.604G>T	p.Asp202Tyr	missense_variant	Exon 7 of 8	1	NM_007283.7	ENSP00000265052.5		A0A0C4DFN3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152192

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2090

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.18

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

Eigen

Benign

-0.0071

Eigen_PC

Benign

0.026

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

D;T;D;.;D;D;T

M_CAP

Uncertain

0.095

MetaRNN

Uncertain

0.62

D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.6

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

PhyloP100

4.1

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.3

D;N;D;D;D;.;N

REVEL

Uncertain

0.38

Sift

Benign

0.21

T;D;T;T;T;.;D

Sift4G

Benign

0.10

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

Polyphen

0.21, 0.79

.;.;B;B;P;.;.

Vest4

0.56

MutPred

0.66

.;.;Gain of methylation at K188 (P = 0.0354);Gain of methylation at K188 (P = 0.0354);.;Gain of methylation at K188 (P = 0.0354);.;

MVP

0.89

MPC

0.57

ClinPred

0.94

GERP RS

5.0

Varity_R

0.58

gMVP

0.59

Mutation Taster

=50/50

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over