rs775337048

Variant names:

• chr3-127695187-C-A
• rs775337048
• NM_007283.7:c.604G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-127695187-C-A
• chr3-127695187-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007283.7(MGLL):​c.604G>T​(p.Asp202Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MGLL NM_007283.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.604G>T	p.Asp202Tyr	missense_variant	Exon 7 of 8	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.604G>T	p.Asp202Tyr	missense_variant	Exon 7 of 8	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152192 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74352

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Benign	0.75
DEOGEN2	Benign	0.18	.;.;T;T;.;.;T
Eigen	Benign	-0.0071
Eigen_PC	Benign	0.026
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D;T;D;.;D;D;T
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.6	.;.;L;L;.;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.3	D;N;D;D;D;.;N
REVEL	Uncertain	0.38
Sift	Benign	0.21	T;D;T;T;T;.;D
Sift4G	Benign	0.10	T;T;T;T;T;.;T
Polyphen		0.21, 0.79	.;.;B;B;P;.;.
Vest4		0.56
MutPred		0.66		.;.;Gain of methylation at K188 (P = 0.0354);Gain of methylation at K188 (P = 0.0354);.;Gain of methylation at K188 (P = 0.0354);.;
MVP		0.89
MPC		0.57
ClinPred		0.94	D
GERP RS		5.0
Varity_R		0.58
gMVP		0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs775337048; hg19: chr3-127414030;