rs594323

Variant names:

• chr3-127730143-G-A
• rs594323
• NM_007283.7:c.263-7577C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-127730143-G-A
• chr3-127730143-G-T

Variant summary

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

The NM_007283.7(MGLL):​c.263-7577C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,066 control chromosomes in the GnomAD database, including 22,492 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 0.53 (22492 hom., cov: 32)
• Consequence: MGLL NM_007283.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 4 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]

ENSG00000302381 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 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.263-7577C>T		intron	N/A	NP_009214.1
	MGLL	NM_001388312.1		c.263-7577C>T		intron	N/A	NP_001375241.1
	MGLL	NM_001388313.1		c.233-7577C>T		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.263-7577C>T		intron	N/A	ENSP00000265052.5
	MGLL	ENST00000398101.7	TSL:1	n.653+5562C>T		intron	N/A
	MGLL	ENST00000479967.5	TSL:1	n.355-7577C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80703 AN: 151948 Hom.: 22465 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.531 AC: 80782 AN: 152066 Hom.: 22492 Cov.: 32 AF XY: 0.530 AC XY: 39387 AN XY: 74312

African (AFR) AF: 0.702 AC: 29109 AN: 41478

American (AMR) AF: 0.464 AC: 7087 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1873 AN: 3464

East Asian (EAS) AF: 0.606 AC: 3126 AN: 5160

South Asian (SAS) AF: 0.534 AC: 2571 AN: 4812

European-Finnish (FIN) AF: 0.445 AC: 4700 AN: 10556

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30441 AN: 68006

Other (OTH) AF: 0.552 AC: 1164 AN: 2108

Alfa AF: 0.476 Hom.: 47703

Bravo AF: 0.542

Asia WGS AF: 0.588 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.1
DANN	Benign	0.66
PhyloP100		-2.0
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: rs594323; hg19: chr3-127448986;