3-127821792-C-T

Variant names:

• chr3-127821792-C-T
• rs11538698
• NM_007283.7:c.57G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_007283.7(MGLL):​c.57G>A​(p.Arg19Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 1,613,988 control chromosomes in the GnomAD database, including 1,135 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 0.028 (90 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1045 hom.)
• Consequence: MGLL NM_007283.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 7 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]

ENSG00000287143 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=1.29 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0279 (4241/152212) while in subpopulation NFE AF = 0.0408 (2773/67992). AF 95% confidence interval is 0.0395. There are 90 homozygotes in GnomAd4. There are 2062 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 90 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.57G>A	p.Arg19Arg	synonymous_variant	Exon 2 of 8	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.57G>A	p.Arg19Arg	synonymous_variant	Exon 2 of 8	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4241 AN: 152096 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.00734

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0408

Gnomad OTH AF: 0.0230

GnomAD2 exomes AF: 0.0294 AC: 7332 AN: 249522 AF XY: 0.0298

Gnomad AFR exome AF: 0.00575

Gnomad AMR exome AF: 0.0174

Gnomad ASJ exome AF: 0.0487

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.0409

Gnomad NFE exome AF: 0.0418

Gnomad OTH exome AF: 0.0327

GnomAD4 exome AF: 0.0362 AC: 52944 AN: 1461776 Hom.: 1045 Cov.: 31 AF XY: 0.0356 AC XY: 25899 AN XY: 727184

African (AFR) AF: 0.00585 AC: 196 AN: 33480

American (AMR) AF: 0.0186 AC: 831 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0512 AC: 1339 AN: 26128

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0117 AC: 1006 AN: 86252

European-Finnish (FIN) AF: 0.0414 AC: 2211 AN: 53420

Middle Eastern (MID) AF: 0.0241 AC: 139 AN: 5768

European-Non Finnish (NFE) AF: 0.0407 AC: 45231 AN: 1111912

Other (OTH) AF: 0.0329 AC: 1988 AN: 60394

GnomAD4 genome AF: 0.0279 AC: 4241 AN: 152212 Hom.: 90 Cov.: 32 AF XY: 0.0277 AC XY: 2062 AN XY: 74428

African (AFR) AF: 0.00732 AC: 304 AN: 41542

American (AMR) AF: 0.0214 AC: 328 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4820

European-Finnish (FIN) AF: 0.0445 AC: 472 AN: 10602

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0408 AC: 2773 AN: 67992

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0358 Hom.: 104

Bravo AF: 0.0255

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.0385

EpiControl AF: 0.0420

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.0
DANN	Benign	0.88
PhyloP100		1.3
PromoterAI		-0.0094	Neutral
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: rs11538698; hg19: chr3-127540635;