NM_007283.7:c.804C>G

Variant names:

• chr3-127694987-G-C
• NM_007283.7:c.804C>G

Variant summary

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

The NM_007283.7(MGLL):​c.804C>G​(p.Asp268Glu) variant causes a missense change involving the alteration of a non-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: 2.49
• 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.804C>G	p.Asp268Glu	missense	Exon 7 of 8	NP_009214.1	A0A0C4DFN3
	MGLL	NM_001388312.1		c.882C>G	p.Asp294Glu	missense	Exon 8 of 9	NP_001375241.1
	MGLL	NM_001388313.1		c.852C>G	p.Asp284Glu	missense	Exon 8 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.804C>G	p.Asp268Glu	missense	Exon 7 of 8	ENSP00000265052.5	A0A0C4DFN3
	MGLL	ENST00000398101.7	TSL:1	n.1195C>G		non_coding_transcript_exon	Exon 5 of 6
	MGLL	ENST00000476682.1	TSL:1	n.3775C>G		non_coding_transcript_exon	Exon 2 of 3

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	Pathogenic	0.70
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.32
Sift	Benign	0.059	T
Sift4G	Uncertain	0.037	D
Polyphen		0.0070	B
Vest4		0.28
MutPred		0.72		Gain of methylation at K255 (P = 0.0775)
MVP		0.73
MPC		0.51
ClinPred		0.92	D
GERP RS		3.1
Varity_R		0.55
gMVP		0.28
Mutation Taster		=71/29	polymorphism

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: chr3-127413830;