Genetic Variant NM_001347.4:c.2566G>A (chr4-961475-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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:2

Conservation

PhyloP100: -0.152

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3052604.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKQ	NM_001347.4	MANE Select	c.2566G>A	p.Val856Met	missense	Exon 21 of 23	NP_001338.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGKQ	ENST00000273814.8	TSL:1 MANE Select	c.2566G>A	p.Val856Met	missense	Exon 21 of 23	ENSP00000273814.3	P52824
DGKQ	ENST00000932945.1		c.2653G>A	p.Val885Met	missense	Exon 21 of 23	ENSP00000603004.1
DGKQ	ENST00000970135.1		c.2608G>A	p.Val870Met	missense	Exon 21 of 23	ENSP00000640194.1

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

GnomAD2 exomes

AF:

0.00118

AC:

254

AN:

216102

AF XY:

0.000831

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 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

African (AFR)

AF:

0.00

AC:

AN:

33010

American (AMR)

AF:

0.00686

AC:

299

AN:

43602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25880

East Asian (EAS)

AF:

0.00

AC:

AN:

38652

South Asian (SAS)

AF:

0.00

AC:

AN:

84518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49298

Middle Eastern (MID)

AF:

0.000418

AC:

AN:

4782

European-Non Finnish (NFE)

AF:

0.00000904

AC:

AN:

1106588

Other (OTH)

AF:

0.000302

AC:

AN:

59610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000296

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41554

American (AMR)

AF:

0.00261

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67976

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000267

Hom.:

Bravo

AF:

0.000767

ExAC

AF:

0.000668

AC:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

DGKQ-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.2

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0080

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.74

PhyloP100

-0.15

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

REVEL

Benign

0.061

Sift

Benign

0.25

Sift4G

Benign

0.20

Polyphen

0.94

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

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over