chr3-127692227-C-T

Variant names:

• chr3-127692227-C-T
• rs2075261232
• NM_007283.7:c.913G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007283.7(MGLL):​c.913G>A​(p.Ala305Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MGLL NM_007283.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.112
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051731527).

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.913G>A	p.Ala305Thr	missense	Exon 8 of 8	NP_009214.1	A0A0C4DFN3
	MGLL	NM_001388312.1		c.991G>A	p.Ala331Thr	missense	Exon 9 of 9	NP_001375241.1
	MGLL	NM_001388313.1		c.961G>A	p.Ala321Thr	missense	Exon 9 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.913G>A	p.Ala305Thr	missense	Exon 8 of 8	ENSP00000265052.5	A0A0C4DFN3
	MGLL	ENST00000398101.7	TSL:1	n.1304G>A		non_coding_transcript_exon	Exon 6 of 6
	MGLL	ENST00000476682.1	TSL:1	n.3884G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

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	Benign	0.081
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.1
DANN	Benign	0.95
DEOGEN2	Benign	0.082	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.074	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.78	N
PhyloP100		-0.11
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.034
Sift	Benign	0.10	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.053
MutPred		0.29		Gain of glycosylation at T296 (P = 0.0316)
MVP		0.061
MPC		0.43
ClinPred		0.079	T
GERP RS		3.2
Varity_R		0.035
gMVP		0.19
Mutation Taster		=97/3	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

dbSNP: rs2075261232; hg19: chr3-127411070; COSMIC: COSV54031244;