Variant 3-186272307-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.82 ( 51182 hom., cov: 33)

Exomes 𝑓: 0.79 ( 451814 hom. )

Consequence

DGKG
NM_001346.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

Variant links:

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]

DGKG links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DGKG	NM_001346.3 link	c.947G>A	p.Arg316Lys	missense_variant	11/25	ENST00000265022.8	NP_001337.2	P49619-1
DGKG	NM_001080744.2 link	c.947G>A	p.Arg316Lys	missense_variant	11/24		NP_001074213.1	P49619-2
DGKG	NM_001080745.2 link	c.947G>A	p.Arg316Lys	missense_variant	11/24		NP_001074214.1	P49619-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKG	ENST00000265022.8 link	c.947G>A	p.Arg316Lys	missense_variant	11/25	1	NM_001346.3	ENSP00000265022.3		P49619-1

Frequencies

GnomAD3 genomes

AF:

0.818

AC:

124409

AN:

152086

Hom.:

51124

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.791

AC:

198808

AN:

251186

Hom.:

79031

AF XY:

0.785

AC XY:

106552

AN XY:

135774

show subpopulations

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 SAS exome

AF:

0.743

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.:

AF XY:

0.784

AC XY:

569286

AN XY:

726588

show subpopulations

Gnomad4 AFR exome

AF:

0.902

Gnomad4 AMR exome

AF:

0.834

Gnomad4 ASJ exome

AF:

0.744

Gnomad4 EAS exome

AF:

0.693

Gnomad4 SAS exome

AF:

0.742

Gnomad4 FIN exome

AF:

0.814

Gnomad4 NFE exome

AF:

0.787

Gnomad4 OTH exome

AF:

0.778

GnomAD4 genome

AF:

0.818

AC:

124528

AN:

152204

Hom.:

51182

Cov.:

AF XY:

0.817

AC XY:

60796

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.896

Gnomad4 AMR

AF:

0.824

Gnomad4 ASJ

AF:

0.752

Gnomad4 EAS

AF:

0.727

Gnomad4 SAS

AF:

0.737

Gnomad4 FIN

AF:

0.806

Gnomad4 NFE

AF:

0.789

Gnomad4 OTH

AF:

0.799

Alfa

AF:

0.787

Hom.:

123616

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

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.25

T;.;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.16

T;T;T;T

MetaRNN

Benign

7.5e-7

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.70

N;N;N;.

PrimateAI

Uncertain

0.53

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

GERP RS

3.9

Varity_R

0.088

gMVP

0.18

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over