3-186281095-T-C

Variant names:

• chr3-186281095-T-C
• rs2239626
• NM_001346.3:c.595-351A>G

Variant summary

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

The NM_001346.3(DGKG):​c.595-351A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 187,998 control chromosomes in the GnomAD database, including 18,484 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 0.42 (16355 hom., cov: 32)
  • Exomes 𝑓: 0.32 (2129 hom.)
• Consequence: DGKG NM_001346.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 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.595-351A>G		intron	N/A	NP_001337.2
	DGKG	NM_001080744.2		c.595-351A>G		intron	N/A	NP_001074213.1
	DGKG	NM_001080745.2		c.595-351A>G		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.595-351A>G		intron	N/A	ENSP00000265022.3
	DGKG	ENST00000344484.8	TSL:1	c.595-351A>G		intron	N/A	ENSP00000339777.4
	DGKG	ENST00000482566.1	TSL:1	n.165A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63439 AN: 151938 Hom.: 16314 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.317 AC: 11397 AN: 35942 Hom.: 2129 Cov.: 0 AF XY: 0.315 AC XY: 5957 AN XY: 18904

African (AFR) AF: 0.760 AC: 1343 AN: 1768

American (AMR) AF: 0.259 AC: 729 AN: 2820

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 379 AN: 1102

East Asian (EAS) AF: 0.307 AC: 684 AN: 2230

South Asian (SAS) AF: 0.316 AC: 1178 AN: 3722

European-Finnish (FIN) AF: 0.218 AC: 312 AN: 1428

Middle Eastern (MID) AF: 0.379 AC: 50 AN: 132

European-Non Finnish (NFE) AF: 0.294 AC: 6123 AN: 20826

Other (OTH) AF: 0.313 AC: 599 AN: 1914

GnomAD4 genome AF: 0.418 AC: 63534 AN: 152056 Hom.: 16355 Cov.: 32 AF XY: 0.409 AC XY: 30400 AN XY: 74360

African (AFR) AF: 0.738 AC: 30617 AN: 41466

American (AMR) AF: 0.305 AC: 4662 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1198 AN: 3468

East Asian (EAS) AF: 0.307 AC: 1586 AN: 5172

South Asian (SAS) AF: 0.315 AC: 1518 AN: 4818

European-Finnish (FIN) AF: 0.225 AC: 2383 AN: 10580

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20369 AN: 67972

Other (OTH) AF: 0.402 AC: 849 AN: 2114

Alfa AF: 0.339 Hom.: 37152

Bravo AF: 0.442

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.2
DANN	Benign	0.76
PhyloP100		-0.63
PromoterAI		-0.00010	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2239626; hg19: chr3-185998884;