dbSNP rs201971574: DGKQ:p.Val856Leu (chr4-961475-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001347.4(DGKQ):c.2566G>T(p.Val856Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,445,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V856M) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DGKQ
NM_001347.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.09829149).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKQ	NM_001347.4 link	c.2566G>T	p.Val856Leu	missense_variant	Exon 21 of 23	ENST00000273814.8	NP_001338.2	P52824Q59FF7A0A140VKC1
DGKQ	XM_047449687.1 link	c.2653G>T	p.Val885Leu	missense_variant	Exon 21 of 23		XP_047305643.1
DGKQ	XM_011513411.2 link	c.2566G>T	p.Val856Leu	missense_variant	Exon 21 of 23		XP_011511713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DGKQ	ENST00000273814.8 link	c.2566G>T	p.Val856Leu	missense_variant	Exon 21 of 23	1	NM_001347.4	ENSP00000273814.3	P52824
DGKQ	ENST00000509465.5 link	c.2365G>T	p.Val789Leu	missense_variant	Exon 20 of 22	5		ENSP00000425862.1	H0YA20
DGKQ	ENST00000515182.1 link	c.211G>T	p.Val71Leu	missense_variant	Exon 3 of 5	5		ENSP00000421756.1	H0Y8Q7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1445948

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718626

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:

0.0000237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.043

MetaRNN

Benign

0.098

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.96

L;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.050

Sift

Benign

0.089

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.84

P;.

Vest4

0.28

MutPred

0.50

Loss of MoRF binding (P = 0.1278);.;

MVP

0.18

MPC

0.19

ClinPred

0.23

GERP RS

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.099

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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