rs13076593

Variant names:

• chr3-127779683-C-G
• rs13076593
• NM_007283.7:c.262+2106G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007283.7(MGLL):​c.262+2106G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 152,206 control chromosomes in the GnomAD database, including 765 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.091 (765 hom., cov: 33)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

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.262+2106G>C		intron	N/A	NP_009214.1	A0A0C4DFN3
	MGLL	NM_001388312.1		c.262+2106G>C		intron	N/A	NP_001375241.1
	MGLL	NM_001388313.1		c.232+2106G>C		intron	N/A	NP_001375242.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGLL	ENST00000265052.10	TSL:1 MANE Select	c.262+2106G>C		intron	N/A	ENSP00000265052.5	A0A0C4DFN3
	MGLL	ENST00000479967.5	TSL:1	n.354+2106G>C		intron	N/A
	MGLL	ENST00000959996.1		c.691+2106G>C		intron	N/A	ENSP00000630055.1

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13863 AN: 152088 Hom.: 764 Cov.: 33

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0766

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0912 AC: 13882 AN: 152206 Hom.: 765 Cov.: 33 AF XY: 0.0931 AC XY: 6929 AN XY: 74422

African (AFR) AF: 0.0519 AC: 2156 AN: 41516

American (AMR) AF: 0.134 AC: 2047 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3472

East Asian (EAS) AF: 0.0407 AC: 211 AN: 5182

South Asian (SAS) AF: 0.148 AC: 711 AN: 4820

European-Finnish (FIN) AF: 0.0658 AC: 698 AN: 10602

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7341 AN: 68002

Other (OTH) AF: 0.0772 AC: 163 AN: 2112

Alfa AF: 0.0934 Hom.: 82

Bravo AF: 0.0894

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.81
DANN	Benign	0.44
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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: rs13076593; hg19: chr3-127498526;