rs376576148

Variant names:

• chr3-127721107-C-A
• rs376576148
• NM_007283.7:c.456G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-127721107-C-A
• chr3-127721107-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007283.7(MGLL):​c.456G>T​(p.Met152Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: 33)
• Consequence: MGLL NM_007283.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40777433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.456G>T	p.Met152Ile	missense_variant	Exon 5 of 8	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.456G>T	p.Met152Ile	missense_variant	Exon 5 of 8	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.054	.;.;T;T;T;.;.;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D;D;D;.;D;D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.41	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.94	.;.;L;L;.;.;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.95	N;N;N;N;N;N;.;N;N
REVEL	Benign	0.095
Sift	Benign	0.033	D;D;D;D;T;D;.;D;T
Sift4G	Benign	0.23	T;T;T;T;T;T;.;T;.
Polyphen		0.080, 0.033	.;.;B;B;.;B;.;.;.
Vest4		0.66
MutPred		0.61		.;.;Loss of catalytic residue at M142 (P = 0.028);Loss of catalytic residue at M142 (P = 0.028);.;.;Loss of catalytic residue at M142 (P = 0.028);.;.;
MVP		0.59
MPC		0.51
ClinPred		0.63	D
GERP RS		4.6
Varity_R		0.34
gMVP		0.59

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: rs376576148; hg19: chr3-127439950;