Variant 3-186253181-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001346.3(DGKG):c.1512T>C(p.Asp504=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,613,704 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 8 hom. )

Consequence

DGKG
NM_001346.3 splice_region, synonymous

Scores

Splicing: ADA: 0.001107

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.241

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 3-186253181-A-G is Benign according to our data. Variant chr3-186253181-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2654332.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.241 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DGKG	NM_001346.3 linkuse as main transcript	c.1512T>C	p.Asp504=	splice_region_variant, synonymous_variant	18/25	ENST00000265022.8
DGKG	NM_001080744.2 linkuse as main transcript	c.1437T>C	p.Asp479=	splice_region_variant, synonymous_variant	17/24
DGKG	NM_001080745.2 linkuse as main transcript	c.1395T>C	p.Asp465=	splice_region_variant, synonymous_variant	17/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKG	ENST00000265022.8 linkuse as main transcript	c.1512T>C	p.Asp504=	splice_region_variant, synonymous_variant	18/25	1	NM_001346.3	P1	P49619-1
DGKG	ENST00000344484.8 linkuse as main transcript	c.1437T>C	p.Asp479=	splice_region_variant, synonymous_variant	17/24	1			P49619-2
DGKG	ENST00000480809.5 linkuse as main transcript	n.1775T>C		splice_region_variant, non_coding_transcript_exon_variant	17/24	1
DGKG	ENST00000382164.8 linkuse as main transcript	c.1395T>C	p.Asp465=	splice_region_variant, synonymous_variant	17/24	5			P49619-3

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

314

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00328

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00225

AC:

567

AN:

251468

Hom.:

AF XY:

0.00235

AC XY:

320

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00378

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00339

AC:

4950

AN:

1461394

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

2426

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.00662

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00401

Gnomad4 OTH exome

AF:

0.00364

GnomAD4 genome

AF:

0.00206

AC:

314

AN:

152310

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00328

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00356

Hom.:

Bravo

AF:

0.00210

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00354

EpiControl

AF:

0.00522

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

DGKG: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

9.3

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0011

dbscSNV1_RF

Benign

0.062

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