3-127781809-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.242T>A	p.Leu81Gln	missense_variant	Exon 3 of 8	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.242T>A	p.Leu81Gln	missense_variant	Exon 3 of 8	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.242T>A (p.L81Q) alteration is located in exon 3 (coding exon 3) of the MGLL gene. This alteration results from a T to A substitution at nucleotide position 242, causing the leucine (L) at amino acid position 81 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.;T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;.;D;D;D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.70	D;D;D;D;D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	2.0	.;.;M;M;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.6	D;D;D;D;.;D;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0020	D;D;D;D;.;D;D
Sift4G	Uncertain	0.021	D;D;D;D;.;.;.
Polyphen		1.0	.;.;D;D;.;.;.
Vest4		0.75
MutPred		0.45		.;.;Loss of stability (P = 0.0322);Loss of stability (P = 0.0322);Loss of stability (P = 0.0322);.;Loss of stability (P = 0.0322);
MVP		0.88
MPC		0.99
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.94
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-127500652;