NM_007283.7:c.242T>A

Variant names:

• chr3-127781809-A-T
• NM_007283.7:c.242T>A

Variant summary

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

The NM_007283.7(MGLL):​c.242T>A​(p.Leu81Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MGLL NM_007283.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.94
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007283.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGLL	NM_007283.7	MANE Select	c.242T>A	p.Leu81Gln	missense	Exon 3 of 8	NP_009214.1	A0A0C4DFN3
	MGLL	NM_001388312.1		c.242T>A	p.Leu81Gln	missense	Exon 3 of 9	NP_001375241.1
	MGLL	NM_001388313.1		c.212T>A	p.Leu71Gln	missense	Exon 3 of 9	NP_001375242.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGLL	ENST00000265052.10	TSL:1 MANE Select	c.242T>A	p.Leu81Gln	missense	Exon 3 of 8	ENSP00000265052.5	A0A0C4DFN3
	MGLL	ENST00000479967.5	TSL:1	n.334T>A		non_coding_transcript_exon	Exon 3 of 6
	MGLL	ENST00000959996.1		c.671T>A	p.Leu224Gln	missense	Exon 5 of 11	ENSP00000630055.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.45		Loss of stability (P = 0.0322)
MVP		0.88
MPC		0.99
ClinPred		0.98	D
GERP RS		5.2
PromoterAI		-0.14	Neutral
Varity_R		0.94
gMVP		0.73
Mutation Taster		=32/68	disease causing

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

Other links and lift over

hg19: chr3-127500652;