chr3-186318664-C-T

Variant names:

• chr3-186318664-C-T
• rs1544702
• NM_001346.3:c.67+1729G>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+1729G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,998 control chromosomes in the GnomAD database, including 4,228 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 0.23 (4228 hom., cov: 31)
• Consequence: DGKG NM_001346.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKG	NM_001346.3	c.67+1729G>A		intron_variant	Intron 2 of 24	ENST00000265022.8	NP_001337.2
DGKG	NM_001080744.2	c.67+1729G>A		intron_variant	Intron 2 of 23		NP_001074213.1
DGKG	NM_001080745.2	c.67+1729G>A		intron_variant	Intron 2 of 23		NP_001074214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKG	ENST00000265022.8	c.67+1729G>A		intron_variant	Intron 2 of 24	1	NM_001346.3	ENSP00000265022.3

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35460 AN: 151880 Hom.: 4208 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.234 AC: 35530 AN: 151998 Hom.: 4228 Cov.: 31 AF XY: 0.234 AC XY: 17417 AN XY: 74290

African (AFR) AF: 0.279 AC: 11548 AN: 41442

American (AMR) AF: 0.202 AC: 3087 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3466

East Asian (EAS) AF: 0.188 AC: 971 AN: 5164

South Asian (SAS) AF: 0.169 AC: 812 AN: 4816

European-Finnish (FIN) AF: 0.273 AC: 2882 AN: 10554

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15071 AN: 67970

Other (OTH) AF: 0.249 AC: 525 AN: 2108

Alfa AF: 0.227 Hom.: 3322

Bravo AF: 0.232

Asia WGS AF: 0.198 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.62
PhyloP100		-2.0
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: rs1544702; hg19: chr3-186036453; COSMIC: COSV53964311;