NM_001346.3:c.1269+81C>T

Variant names:

• chr3-186265166-G-A
• rs3815620
• NM_001346.3:c.1269+81C>T

Variant summary

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

The NM_001346.3(DGKG):​c.1269+81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,375,404 control chromosomes in the GnomAD database, including 238,347 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 0.56 (24087 hom., cov: 32)
  • Exomes 𝑓: 0.59 (214260 hom.)
• Consequence: DGKG NM_001346.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKG	NM_001346.3	MANE Select	c.1269+81C>T		intron	N/A	NP_001337.2
	DGKG	NM_001080744.2		c.1269+81C>T		intron	N/A	NP_001074213.1
	DGKG	NM_001080745.2		c.1152+81C>T		intron	N/A	NP_001074214.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKG	ENST00000265022.8	TSL:1 MANE Select	c.1269+81C>T		intron	N/A	ENSP00000265022.3
	DGKG	ENST00000344484.8	TSL:1	c.1269+81C>T		intron	N/A	ENSP00000339777.4
	DGKG	ENST00000480809.5	TSL:1	n.1532+81C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84846 AN: 151942 Hom.: 24072 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.590 AC: 721867 AN: 1223344 Hom.: 214260 AF XY: 0.588 AC XY: 363773 AN XY: 618422

African (AFR) AF: 0.444 AC: 12834 AN: 28874

American (AMR) AF: 0.624 AC: 27059 AN: 43370

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 13367 AN: 24588

East Asian (EAS) AF: 0.680 AC: 26104 AN: 38408

South Asian (SAS) AF: 0.528 AC: 42731 AN: 80966

European-Finnish (FIN) AF: 0.569 AC: 29822 AN: 52410

Middle Eastern (MID) AF: 0.605 AC: 3219 AN: 5320

European-Non Finnish (NFE) AF: 0.598 AC: 536128 AN: 896946

Other (OTH) AF: 0.583 AC: 30603 AN: 52462

GnomAD4 genome AF: 0.558 AC: 84905 AN: 152060 Hom.: 24087 Cov.: 32 AF XY: 0.558 AC XY: 41481 AN XY: 74326

African (AFR) AF: 0.453 AC: 18774 AN: 41474

American (AMR) AF: 0.607 AC: 9278 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1936 AN: 3470

East Asian (EAS) AF: 0.702 AC: 3620 AN: 5156

South Asian (SAS) AF: 0.523 AC: 2523 AN: 4824

European-Finnish (FIN) AF: 0.553 AC: 5848 AN: 10568

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40951 AN: 67962

Other (OTH) AF: 0.581 AC: 1224 AN: 2106

Alfa AF: 0.582 Hom.: 36983

Bravo AF: 0.558

Asia WGS AF: 0.645 AC: 2237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		0.062
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: rs3815620; hg19: chr3-185982955;