7-6447809-C-T

Position:

• chr7-6447809-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000297056.11(DAGLB):​c.34G>A​(p.Ala12Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,976 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DAGLB ENST00000297056.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03

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]

DAGLB (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25316334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAGLB	NM_139179.4	c.34G>A	p.Ala12Thr	missense_variant	1/15	ENST00000297056.11	NP_631918.3
DAGLB	NM_001142936.2	c.34G>A	p.Ala12Thr	missense_variant	1/13		NP_001136408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAGLB	ENST00000297056.11	c.34G>A	p.Ala12Thr	missense_variant	1/15	1	NM_139179.4	ENSP00000297056.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460976 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726796

Gnomad4 AFR exome AF: 0.00

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: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.34G>A (p.A12T) alteration is located in exon 1 (coding exon 1) of the DAGLB gene. This alteration results from a G to A substitution at nucleotide position 34, causing the alanine (A) at amino acid position 12 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;.;T
Eigen	Benign	0.087
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;.
MutationTaster	Benign	0.56	D;D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.66	N;N;N
REVEL	Benign	0.052
Sift	Uncertain	0.0080	D;T;T
Sift4G	Benign	0.18	T;T;.
Polyphen		0.48	P;.;.
Vest4		0.44
MutPred		0.37		Loss of catalytic residue at A12 (P = 0.0366);Loss of catalytic residue at A12 (P = 0.0366);Loss of catalytic residue at A12 (P = 0.0366);
MVP		0.54
MPC		0.076
ClinPred		0.90	D
GERP RS		4.4
Varity_R		0.13
gMVP		0.47

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: chr7-6487440;