rs371817663

Variant names:

• chr3-127695094-C-A
• NM_007283.7:c.697G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-127695094-C-A
• chr3-127695094-C-G
• chr3-127695094-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007283.7(MGLL):​c.697G>T​(p.Ala233Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MGLL NM_007283.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31263044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.697G>T	p.Ala233Ser	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.697G>T	p.Ala233Ser	missense_variant	Exon 7 of 8	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461846 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.049	.;.;T;T;.;.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.023
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.85	T;T;T;.;T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.31	T;T;T;T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.66	.;.;N;N;.;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.18	N;N;N;N;N;.;N
REVEL	Benign	0.16
Sift	Benign	0.70	T;T;T;T;T;.;T
Sift4G	Benign	0.71	T;T;T;T;T;.;T
Polyphen		0.0070, 0.12	.;.;B;B;B;.;.
Vest4		0.096
MutPred		0.64		.;.;Gain of disorder (P = 0.0466);Gain of disorder (P = 0.0466);.;Gain of disorder (P = 0.0466);.;
MVP		0.82
MPC		0.42
ClinPred		0.88	D
GERP RS		5.0
Varity_R		0.31
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-127413937;