Variant chr3-186251868-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001346.3(DGKG):c.1652C>G(p.Pro551Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000823 in 1,458,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P551S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

DGKG
NM_001346.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17805222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DGKG	NM_001346.3 linkuse as main transcript	c.1652C>G	p.Pro551Arg	missense_variant	19/25	ENST00000265022.8
DGKG	NM_001080744.2 linkuse as main transcript	c.1577C>G	p.Pro526Arg	missense_variant	18/24
DGKG	NM_001080745.2 linkuse as main transcript	c.1535C>G	p.Pro512Arg	missense_variant	18/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKG	ENST00000265022.8 linkuse as main transcript	c.1652C>G	p.Pro551Arg	missense_variant	19/25	1	NM_001346.3	P1	P49619-1
DGKG	ENST00000344484.8 linkuse as main transcript	c.1577C>G	p.Pro526Arg	missense_variant	18/24	1			P49619-2
DGKG	ENST00000480809.5 linkuse as main transcript	n.1915C>G		non_coding_transcript_exon_variant	18/24	1
DGKG	ENST00000382164.8 linkuse as main transcript	c.1535C>G	p.Pro512Arg	missense_variant	18/24	5			P49619-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248254

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000823

AC:

AN:

1458628

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725466

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000721

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

The c.1652C>G (p.P551R) alteration is located in exon 19 (coding exon 18) of the DGKG gene. This alteration results from a C to G substitution at nucleotide position 1652, causing the proline (P) at amino acid position 551 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.089

T;.;.

Eigen

Benign

-0.25

Eigen_PC

Benign

0.0089

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.0063

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.82

N;.;.

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.46

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.36

T;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.83

P;B;B

Vest4

0.43

MVP

0.51

MPC

0.28

ClinPred

0.63

GERP RS

5.1

Varity_R

0.18

gMVP

0.44

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over