3-127720095-C-T

Variant names:

• chr3-127720095-C-T
• rs3773159
• NM_007283.7:c.510+958G>A

Variant summary

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

The NM_007283.7(MGLL):​c.510+958G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,136 control chromosomes in the GnomAD database, including 2,080 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 0.16 (2080 hom., cov: 32)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896
• Publications: 12 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.211 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGLL	NM_007283.7	MANE Select	c.510+958G>A		intron	N/A	NP_009214.1
	MGLL	NM_001388312.1		c.510+958G>A		intron	N/A	NP_001375241.1
	MGLL	NM_001388313.1		c.480+958G>A		intron	N/A	NP_001375242.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGLL	ENST00000265052.10	TSL:1 MANE Select	c.510+958G>A		intron	N/A	ENSP00000265052.5
	MGLL	ENST00000398101.7	TSL:1	n.901+958G>A		intron	N/A
	MGLL	ENST00000479967.5	TSL:1	n.602+958G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24196 AN: 152018 Hom.: 2079 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.159 AC: 24204 AN: 152136 Hom.: 2080 Cov.: 32 AF XY: 0.161 AC XY: 11959 AN XY: 74374

African (AFR) AF: 0.120 AC: 5002 AN: 41518

American (AMR) AF: 0.217 AC: 3320 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3466

East Asian (EAS) AF: 0.133 AC: 689 AN: 5182

South Asian (SAS) AF: 0.168 AC: 810 AN: 4812

European-Finnish (FIN) AF: 0.173 AC: 1825 AN: 10572

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11166 AN: 67992

Other (OTH) AF: 0.210 AC: 444 AN: 2116

Alfa AF: 0.169 Hom.: 3651

Bravo AF: 0.163

Asia WGS AF: 0.160 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.85
DANN	Benign	0.58
PhyloP100		-0.90
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: rs3773159; hg19: chr3-127438938; COSMIC: COSV54023609; COSMIC: COSV54023609;