NM_006133.3:c.856A>T

Variant names:

• chr11-61731323-A-T
• NM_006133.3:c.856A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006133.3(DAGLA):​c.856A>T​(p.Met286Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DAGLA NM_006133.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 8.60
• Publications: 0 publications found

Genes affected

DAGLA (HGNC:1165): (diacylglycerol lipase alpha) This gene encodes a diacylglycerol lipase. The encoded enzyme is involved in the biosynthesis of the endocannabinoid 2-arachidonoyl-glycerol.[provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006133.3. 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
	DAGLA	NM_006133.3	MANE Select	c.856A>T	p.Met286Leu	missense	Exon 9 of 20	NP_006124.1	Q9Y4D2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAGLA	ENST00000257215.10	TSL:1 MANE Select	c.856A>T	p.Met286Leu	missense	Exon 9 of 20	ENSP00000257215.5	Q9Y4D2
	DAGLA	ENST00000875660.1		c.934A>T	p.Met312Leu	missense	Exon 10 of 21	ENSP00000545719.1
	DAGLA	ENST00000939714.1		c.856A>T	p.Met286Leu	missense	Exon 9 of 20	ENSP00000609773.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.068	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.27	N
PhyloP100		8.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.62	N
REVEL	Uncertain	0.34
Sift	Benign	0.34	T
Sift4G	Benign	0.99	T
Polyphen		0.52	P
Vest4		0.67
MutPred		0.43		Loss of methylation at K290 (P = 0.0579)
MVP		0.46
MPC		1.9
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.26
gMVP		0.68
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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

hg19: chr11-61498795;