3-127692247-A-T

Position:

• chr3-127692247-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007283.7(MGLL):​c.893T>A​(p.Met298Lys) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MGLL NM_007283.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07465622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGLL	NM_007283.7	c.893T>A	p.Met298Lys	missense_variant	8/8	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.893T>A	p.Met298Lys	missense_variant	8/8	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	8.1
DANN	Benign	0.56
DEOGEN2	Benign	0.057	.;.;T;T;T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.65	T;T;T;.;T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.075	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.53	.;.;N;N;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.050	N;N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.36	T;T;T;T;T;T;T
Sift4G	Benign	0.88	T;T;T;T;T;T;T
Polyphen		0.0, 0.0020	.;.;B;B;.;B;.
Vest4		0.24
MutPred		0.44		.;.;Loss of stability (P = 0.0032);Loss of stability (P = 0.0032);.;.;.;
MVP		0.061
MPC		0.69
ClinPred		0.063	T
GERP RS		-4.5
Varity_R		0.28
gMVP		0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs11538700; hg19: chr3-127411090;