4-961475-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001347.4(DGKQ):c.2566G>A(p.Val856Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,598,178 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 7 hom. )

Consequence

DGKQ
NM_001347.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.152

Variant links:

Genes affected

DGKQ (HGNC:2856): (diacylglycerol kinase theta) The protein encoded by this gene contains three cysteine-rich domains, a proline-rich region, and a pleckstrin homology domain with an overlapping Ras-associating domain. It is localized in the speckle domains of the nucleus, and mediates the regeneration of phosphatidylinositol (PI) from diacylglycerol in the PI-cycle during cell signal transduction. [provided by RefSeq, Jul 2008]

DGKQ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0079835355).

BP6

Variant 4-961475-C-T is Benign according to our data. Variant chr4-961475-C-T is described in ClinVar as [Benign]. Clinvar id is 3052604.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DGKQ	NM_001347.4 linkuse as main transcript	c.2566G>A	p.Val856Met	missense_variant	21/23	ENST00000273814.8
DGKQ	XM_047449687.1 linkuse as main transcript	c.2653G>A	p.Val885Met	missense_variant	21/23
DGKQ	XM_011513411.2 linkuse as main transcript	c.2566G>A	p.Val856Met	missense_variant	21/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DGKQ	ENST00000273814.8 linkuse as main transcript	c.2566G>A	p.Val856Met	missense_variant	21/23	1	NM_001347.4	P1
DGKQ	ENST00000509465.5 linkuse as main transcript	c.2368G>A	p.Val790Met	missense_variant	20/22	5
DGKQ	ENST00000515182.1 linkuse as main transcript	c.211G>A	p.Val71Met	missense_variant	3/5	5

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00118

AC:

254

AN:

216102

Hom.:

AF XY:

0.000831

AC XY:

AN XY:

119116

show subpopulations

Gnomad AFR exome

AF:

0.0000780

Gnomad AMR exome

AF:

0.00752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000613

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.000746

GnomAD4 exome

AF:

0.000228

AC:

329

AN:

1445940

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

137

AN XY:

718620

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00686

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:

0.00000904

Gnomad4 OTH exome

AF:

0.000302

GnomAD4 genome

AF:

0.000296

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.000767

ExAC

AF:

0.000668

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DGKQ-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 21, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

Cadd

Benign

9.2

Dann

Uncertain

1.0

DEOGEN2

Benign

0.053

T;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.0080

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.74

N;.

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.061

Sift

Benign

0.25

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.94

P;.

Vest4

0.24

MutPred

0.50

Loss of catalytic residue at V856 (P = 0.0056);.;

MVP

0.20

MPC

0.23

ClinPred

0.021

GERP RS

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.048

gMVP

0.45

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