3-186272307-C-T

Variant names:

• chr3-186272307-C-T
• rs2193587
• NM_001346.3:c.947G>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.947G>A​(p.Arg316Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 1,612,738 control chromosomes in the GnomAD database, including 502,996 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (51182 hom., cov: 33)
  • Exomes 𝑓: 0.79 (451814 hom.)
• Consequence: DGKG NM_001346.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 41 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 (MetaRNN=7.5480705E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKG	NM_001346.3	c.947G>A	p.Arg316Lys	missense_variant	Exon 11 of 25	ENST00000265022.8	NP_001337.2
DGKG	NM_001080744.2	c.947G>A	p.Arg316Lys	missense_variant	Exon 11 of 24		NP_001074213.1
DGKG	NM_001080745.2	c.947G>A	p.Arg316Lys	missense_variant	Exon 11 of 24		NP_001074214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKG	ENST00000265022.8	c.947G>A	p.Arg316Lys	missense_variant	Exon 11 of 25	1	NM_001346.3	ENSP00000265022.3

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124409 AN: 152086 Hom.: 51124 Cov.: 33

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.798

GnomAD2 exomes AF: 0.791 AC: 198808 AN: 251186 AF XY: 0.785

Gnomad AFR exome AF: 0.899

Gnomad AMR exome AF: 0.832

Gnomad ASJ exome AF: 0.745

Gnomad EAS exome AF: 0.727

Gnomad FIN exome AF: 0.810

Gnomad NFE exome AF: 0.788

Gnomad OTH exome AF: 0.787

GnomAD4 exome AF: 0.786 AC: 1147325 AN: 1460534 Hom.: 451814 Cov.: 42 AF XY: 0.784 AC XY: 569286 AN XY: 726588

African (AFR) AF: 0.902 AC: 30190 AN: 33464

American (AMR) AF: 0.834 AC: 37255 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 19437 AN: 26114

East Asian (EAS) AF: 0.693 AC: 27504 AN: 39662

South Asian (SAS) AF: 0.742 AC: 63967 AN: 86180

European-Finnish (FIN) AF: 0.814 AC: 43477 AN: 53390

Middle Eastern (MID) AF: 0.781 AC: 4501 AN: 5764

European-Non Finnish (NFE) AF: 0.787 AC: 874079 AN: 1110928

Other (OTH) AF: 0.778 AC: 46915 AN: 60340

GnomAD4 genome AF: 0.818 AC: 124528 AN: 152204 Hom.: 51182 Cov.: 33 AF XY: 0.817 AC XY: 60796 AN XY: 74402

African (AFR) AF: 0.896 AC: 37199 AN: 41536

American (AMR) AF: 0.824 AC: 12600 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2608 AN: 3468

East Asian (EAS) AF: 0.727 AC: 3754 AN: 5166

South Asian (SAS) AF: 0.737 AC: 3553 AN: 4820

European-Finnish (FIN) AF: 0.806 AC: 8538 AN: 10588

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53640 AN: 68018

Other (OTH) AF: 0.799 AC: 1686 AN: 2110

Alfa AF: 0.793 Hom.: 186782

Bravo AF: 0.819

TwinsUK AF: 0.782 AC: 2898

ALSPAC AF: 0.794 AC: 3060

ESP6500AA AF: 0.897 AC: 3951

ESP6500EA AF: 0.788 AC: 6775

ExAC AF: 0.793 AC: 96315

Asia WGS AF: 0.766 AC: 2666 AN: 3478

EpiCase AF: 0.776

EpiControl AF: 0.775

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.70
DEOGEN2	Benign	0.25	T;.;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.16	T;T;T;T
MetaRNN	Benign	7.5e-7	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.70	N;N;N;.
PhyloP100		1.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.22	N;N;N;N
REVEL	Benign	0.25
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.013
MPC		0.073
ClinPred		0.0031	T
GERP RS		3.9
Varity_R		0.088
gMVP		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs2193587; hg19: chr3-185990096; COSMIC: COSV104593405;