rs6786711

Variant names:

• chr3-186350893-C-T
• rs6786711
• NM_001346.3:c.-249+11053G>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.-249+11053G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,124 control chromosomes in the GnomAD database, including 4,127 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 0.19 (4127 hom., cov: 32)
• Consequence: DGKG NM_001346.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKG	NM_001346.3	c.-249+11053G>A		intron_variant	Intron 1 of 24	ENST00000265022.8	NP_001337.2
DGKG	NM_001080744.2	c.-249+11053G>A		intron_variant	Intron 1 of 23		NP_001074213.1
DGKG	NM_001080745.2	c.-249+11053G>A		intron_variant	Intron 1 of 23		NP_001074214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKG	ENST00000265022.8	c.-249+11053G>A		intron_variant	Intron 1 of 24	1	NM_001346.3	ENSP00000265022.3
DGKG	ENST00000344484.8	c.-249+11053G>A		intron_variant	Intron 1 of 23	1		ENSP00000339777.4
DGKG	ENST00000480809.5	n.132+11053G>A		intron_variant	Intron 1 of 23	1
DGKG	ENST00000382164.8	c.-249+11053G>A		intron_variant	Intron 1 of 23	5		ENSP00000371599.4

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29000 AN: 152006 Hom.: 4097 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0520

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.191 AC: 29080 AN: 152124 Hom.: 4127 Cov.: 32 AF XY: 0.188 AC XY: 13985 AN XY: 74382

African (AFR) AF: 0.403 AC: 16740 AN: 41492

American (AMR) AF: 0.114 AC: 1748 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3472

East Asian (EAS) AF: 0.0511 AC: 265 AN: 5184

South Asian (SAS) AF: 0.0846 AC: 408 AN: 4820

European-Finnish (FIN) AF: 0.131 AC: 1390 AN: 10576

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7555 AN: 67988

Other (OTH) AF: 0.187 AC: 394 AN: 2112

Alfa AF: 0.173 Hom.: 2673

Bravo AF: 0.201

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.55
PhyloP100		-0.070
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: rs6786711; hg19: chr3-186068682;