3-127721151-C-T

Variant names:

• chr3-127721151-C-T
• rs201835629
• NM_007283.7:c.412G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_007283.7(MGLL):​c.412G>A​(p.Ala138Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: MGLL NM_007283.7 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.256
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029941916).
• BP6: Variant 3-127721151-C-T is Benign according to our data. Variant chr3-127721151-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2672954.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGLL	NM_007283.7	c.412G>A	p.Ala138Thr	missense_variant	Exon 5 of 8	ENST00000265052.10	NP_009214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGLL	ENST00000265052.10	c.412G>A	p.Ala138Thr	missense_variant	Exon 5 of 8	1	NM_007283.7	ENSP00000265052.5

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000177 AC: 44 AN: 249168 AF XY: 0.000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00388

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000103 AC: 150 AN: 1461802 Hom.: 0 Cov.: 31 AF XY: 0.000100 AC XY: 73 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00417 AC: 109 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111962

Other (OTH) AF: 0.000265 AC: 16 AN: 60394

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74498

African (AFR) AF: 0.00 AC: 0 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000191 Hom.: 1

Bravo AF: 0.0000982

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000239 AC: 2

ExAC AF: 0.000182 AC: 22

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MGLL: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	9.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;.;T;T;T;.;.;T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.87	D;D;D;.;D;D;D;T;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.030	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.9	.;.;L;L;.;.;.;.;.
PhyloP100		0.26
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.2	N;N;N;N;N;N;.;N;N
REVEL	Uncertain	0.58
Sift	Benign	0.084	T;T;T;T;T;D;.;T;T
Sift4G	Benign	0.068	T;T;T;T;T;T;.;T;.
Polyphen		0.87, 0.61	.;.;P;P;.;P;.;.;.
Vest4		0.49
MVP		0.86
MPC		0.47
ClinPred		0.048	T
GERP RS		-7.9
PromoterAI		-0.042	Neutral
Varity_R		0.11
gMVP		0.67
Mutation Taster		=73/27	polymorphism

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: rs201835629; hg19: chr3-127439994;