3-127690066-C-T

Position:

• chr3-127690066-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007283.7(MGLL):​c.*2132G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,010 control chromosomes in the GnomAD database, including 44,902 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 0.77 (44881 hom., cov: 30)
  • Exomes 𝑓: 0.79 (21 hom.)
• Consequence: MGLL NM_007283.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGLL	NM_007283.7	c.*2132G>A		3_prime_UTR_variant	8/8	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.*2132G>A		3_prime_UTR_variant	8/8	1	NM_007283.7	ENSP00000265052.5
MGLL	ENST00000398104.6	c.*2132G>A		3_prime_UTR_variant	8/8	5		ENSP00000381176.1
MGLL	ENST00000453507.7	c.*2132G>A		3_prime_UTR_variant	7/7	2		ENSP00000404146.2

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116304 AN: 151830 Hom.: 44844 Cov.: 30

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.773

GnomAD4 exome AF: 0.790 AC: 49 AN: 62 Hom.: 21 Cov.: 0 AF XY: 0.800 AC XY: 32 AN XY: 40

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.737

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.766 AC: 116393 AN: 151948 Hom.: 44881 Cov.: 30 AF XY: 0.760 AC XY: 56433 AN XY: 74228

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.769

Alfa AF: 0.767 Hom.: 43545

Bravo AF: 0.769

Asia WGS AF: 0.682 AC: 2374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.40

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: rs6439081; hg19: chr3-127408909; COSMIC: COSV54023536; COSMIC: COSV54023536;