NM_139179.4:c.1787T>A

Variant names:

• chr7-6410163-A-T
• rs139753251
• NM_139179.4:c.1787T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_139179.4(DAGLB):​c.1787T>A​(p.Ile596Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,428,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I596T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DAGLB NM_139179.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.11
• Publications: 0 publications found

Genes affected

DAGLB (HGNC:28923): (diacylglycerol lipase beta) Enables lipase activity. Involved in arachidonic acid metabolic process. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139179.4. 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
	DAGLB	NM_139179.4	MANE Select	c.1787T>A	p.Ile596Asn	missense	Exon 14 of 15	NP_631918.3	Q8NCG7-1
	DAGLB	NM_001142936.2		c.1400T>A	p.Ile467Asn	missense	Exon 12 of 13	NP_001136408.1	Q8NCG7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAGLB	ENST00000297056.11	TSL:1 MANE Select	c.1787T>A	p.Ile596Asn	missense	Exon 14 of 15	ENSP00000297056.6	Q8NCG7-1
	DAGLB	ENST00000878465.1		c.1895T>A	p.Ile632Asn	missense	Exon 15 of 16	ENSP00000548524.1
	DAGLB	ENST00000878464.1		c.1781T>A	p.Ile594Asn	missense	Exon 14 of 15	ENSP00000548523.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428624 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 706480

African (AFR) AF: 0.00 AC: 0 AN: 32912

American (AMR) AF: 0.00 AC: 0 AN: 40882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24316

East Asian (EAS) AF: 0.00 AC: 0 AN: 38980

South Asian (SAS) AF: 0.00 AC: 0 AN: 82464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092484

Other (OTH) AF: 0.00 AC: 0 AN: 58924

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	-0.085	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.73		Gain of disorder (P = 0.0269)
MVP		0.81
MPC		0.38
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.89
gMVP		0.94
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

dbSNP: rs139753251; hg19: chr7-6449794;