11-61720167-C-G

Variant names:

• chr11-61720167-C-G
• rs142265242
• NM_006133.3:c.12C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006133.3(DAGLA):​c.12C>G​(p.Ile4Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I4I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DAGLA NM_006133.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07507241).

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.12C>G	p.Ile4Met	missense	Exon 2 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.12C>G	p.Ile4Met	missense	Exon 2 of 20	ENSP00000257215.5	Q9Y4D2
	DAGLA	ENST00000875660.1		c.12C>G	p.Ile4Met	missense	Exon 2 of 21	ENSP00000545719.1
	DAGLA	ENST00000939714.1		c.12C>G	p.Ile4Met	missense	Exon 2 of 20	ENSP00000609773.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	9.8
DANN	Benign	0.65
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.42	N
PhyloP100		0.57
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.20
Sift	Benign	0.41	T
Sift4G	Benign	0.33	T
Polyphen		0.029	B
Vest4		0.24
MutPred		0.52		Gain of disorder (P = 0.0284)
MVP		0.40
MPC		1.1
ClinPred		0.22	T
GERP RS		0.85
Varity_R		0.12
gMVP		0.55
Mutation Taster		=77/23	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: rs142265242; hg19: chr11-61487639;