3-186315613-C-T

Variant names:

• chr3-186315613-C-T
• rs3819847
• NM_001346.3:c.67+4780G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001346.3(DGKG):​c.67+4780G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,444 control chromosomes in the GnomAD database, including 26,001 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (26001 hom., cov: 29)
• Consequence: DGKG NM_001346.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 4 publications found

Genes affected

DGKG (HGNC:2853): (diacylglycerol kinase gamma) This gene encodes an enzyme that is a member of the type I subfamily of diacylglycerol kinases, which are involved in lipid metabolism. These enzymes generate phosphatidic acid by catalyzing the phosphorylation of diacylglycerol, a fundamental lipid second messenger that activates numerous proteins, including protein kinase C isoforms, Ras guanyl nucleotide-releasing proteins and some transient receptor potential channels. Diacylglycerol kinase gamma has been implicated in cell cycle regulation and in the negative regulation of macrophage differentiation in leukemia cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346.3. 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
	DGKG	NM_001346.3	MANE Select	c.67+4780G>A		intron	N/A	NP_001337.2	P49619-1
	DGKG	NM_001080744.2		c.67+4780G>A		intron	N/A	NP_001074213.1	P49619-2
	DGKG	NM_001080745.2		c.67+4780G>A		intron	N/A	NP_001074214.1	P49619-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKG	ENST00000265022.8	TSL:1 MANE Select	c.67+4780G>A		intron	N/A	ENSP00000265022.3	P49619-1
	DGKG	ENST00000344484.8	TSL:1	c.67+4780G>A		intron	N/A	ENSP00000339777.4	P49619-2
	DGKG	ENST00000480809.5	TSL:1	n.447+4780G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87615 AN: 151326 Hom.: 25974 Cov.: 29

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.627

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.579 AC: 87691 AN: 151444 Hom.: 26001 Cov.: 29 AF XY: 0.584 AC XY: 43206 AN XY: 73980

African (AFR) AF: 0.436 AC: 17950 AN: 41184

American (AMR) AF: 0.626 AC: 9541 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2031 AN: 3466

East Asian (EAS) AF: 0.576 AC: 2950 AN: 5124

South Asian (SAS) AF: 0.582 AC: 2798 AN: 4808

European-Finnish (FIN) AF: 0.707 AC: 7394 AN: 10464

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43059 AN: 67846

Other (OTH) AF: 0.628 AC: 1321 AN: 2102

Alfa AF: 0.619 Hom.: 14996

Bravo AF: 0.565

Asia WGS AF: 0.600 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.57
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs3819847; hg19: chr3-186033402;