chr3-127695133-C-T

Variant names:

• chr3-127695133-C-T
• rs138122374
• NM_007283.7:c.658G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_007283.7(MGLL):​c.658G>A​(p.Gly220Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00103 in 1,614,136 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (13 hom.)
• Consequence: MGLL NM_007283.7 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.22
• 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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0077992976).
• BP6: Variant 3-127695133-C-T is Benign according to our data. Variant chr3-127695133-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3042845.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

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.658G>A	p.Gly220Ser	missense	Exon 7 of 8	NP_009214.1	A0A0C4DFN3
	MGLL	NM_001388312.1		c.736G>A	p.Gly246Ser	missense	Exon 8 of 9	NP_001375241.1
	MGLL	NM_001388313.1		c.706G>A	p.Gly236Ser	missense	Exon 8 of 9	NP_001375242.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGLL	ENST00000265052.10	TSL:1 MANE Select	c.658G>A	p.Gly220Ser	missense	Exon 7 of 8	ENSP00000265052.5	A0A0C4DFN3
	MGLL	ENST00000398101.7	TSL:1	n.1049G>A		non_coding_transcript_exon	Exon 5 of 6
	MGLL	ENST00000476682.1	TSL:1	n.3629G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.00147 AC: 223 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00621

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00311 AC: 777 AN: 249442 AF XY: 0.00272

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.0114

Gnomad ASJ exome AF: 0.000993

Gnomad EAS exome AF: 0.0124

Gnomad FIN exome AF: 0.00311

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.000988 AC: 1444 AN: 1461846 Hom.: 13 Cov.: 32 AF XY: 0.000939 AC XY: 683 AN XY: 727232

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.0110 AC: 492 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000727 AC: 19 AN: 26136

East Asian (EAS) AF: 0.0106 AC: 422 AN: 39700

South Asian (SAS) AF: 0.00153 AC: 132 AN: 86256

European-Finnish (FIN) AF: 0.00326 AC: 174 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000117 AC: 130 AN: 1112008

Other (OTH) AF: 0.00121 AC: 73 AN: 60396

GnomAD4 genome AF: 0.00147 AC: 224 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.00168 AC XY: 125 AN XY: 74464

African (AFR) AF: 0.0000481 AC: 2 AN: 41554

American (AMR) AF: 0.00621 AC: 95 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.0125 AC: 65 AN: 5184

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4818

European-Finnish (FIN) AF: 0.00301 AC: 32 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68030

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.00201

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000357 AC: 3

ExAC AF: 0.00251 AC: 304

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MGLL-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.0078	T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.36
Sift	Benign	0.42	T
Sift4G	Benign	0.17	T
Polyphen		0.86	P
Vest4		0.50
MVP		0.86
MPC		0.60
ClinPred		0.025	T
GERP RS		5.0
Varity_R		0.49
gMVP		0.78
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs138122374; hg19: chr3-127413976; COSMIC: COSV54022868;