rs2193587

Positions:

• chr3-186272307-C-A
• chr3-186272307-C-G
• chr3-186272307-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001346.3(DGKG):​c.947G>T​(p.Arg316Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R316K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DGKG NM_001346.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKG	NM_001346.3	c.947G>T	p.Arg316Ile	missense_variant	11/25	ENST00000265022.8	NP_001337.2
DGKG	NM_001080744.2	c.947G>T	p.Arg316Ile	missense_variant	11/24		NP_001074213.1
DGKG	NM_001080745.2	c.947G>T	p.Arg316Ile	missense_variant	11/24		NP_001074214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKG	ENST00000265022.8	c.947G>T	p.Arg316Ile	missense_variant	11/25	1	NM_001346.3	ENSP00000265022	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.74	D;.;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.77	T;T;D;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.68	D;D;D;D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Uncertain	2.7	M;M;M;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.7	D;D;D;D
REVEL	Uncertain	0.45
Sift	Benign	0.044	D;D;D;D
Sift4G	Uncertain	0.036	D;D;T;D
Polyphen		0.84	P;P;P;.
Vest4		0.21
MutPred		0.65		Loss of solvent accessibility (P = 3e-04);Loss of solvent accessibility (P = 3e-04);Loss of solvent accessibility (P = 3e-04);.;
MVP		0.89
MPC		0.18
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.39
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2193587; hg19: chr3-185990096;