chr4-961105-C-T

Position:

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001347.4(DGKQ):​c.2671G>A​(p.Gly891Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

DGKQ
NM_001347.4 missense

Scores

17
1
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.991

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DGKQNM_001347.4 linkuse as main transcriptc.2671G>A p.Gly891Arg missense_variant 22/23 ENST00000273814.8 NP_001338.2
DGKQXM_047449687.1 linkuse as main transcriptc.2758G>A p.Gly920Arg missense_variant 22/23 XP_047305643.1
DGKQXM_011513411.2 linkuse as main transcriptc.2671G>A p.Gly891Arg missense_variant 22/23 XP_011511713.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DGKQENST00000273814.8 linkuse as main transcriptc.2671G>A p.Gly891Arg missense_variant 22/231 NM_001347.4 ENSP00000273814 P1
DGKQENST00000509465.5 linkuse as main transcriptc.2473G>A p.Gly825Arg missense_variant 21/225 ENSP00000425862
DGKQENST00000515182.1 linkuse as main transcriptc.316G>A p.Gly106Arg missense_variant 4/55 ENSP00000421756

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000812
AC:
2
AN:
246400
Hom.:
0
AF XY:
0.00000747
AC XY:
1
AN XY:
133924
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:
0.0000182
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1459648
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
726134
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:
0.0000192
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
ExAC
AF:
0.00000825
AC:
1

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 submitterclinical testingAmbry GeneticsDec 04, 2023The c.2671G>A (p.G891R) alteration is located in exon 22 (coding exon 22) of the DGKQ gene. This alteration results from a G to A substitution at nucleotide position 2671, causing the glycine (G) at amino acid position 891 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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.46
D
BayesDel_noAF
Pathogenic
0.44
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.44
T;.
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.97
D;D
M_CAP
Pathogenic
0.86
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
4.1
H;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-7.4
D;D
REVEL
Pathogenic
0.94
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.88
MutPred
0.93
Gain of MoRF binding (P = 0.1939);.;
MVP
0.98
MPC
0.63
ClinPred
1.0
D
GERP RS
5.2
Varity_R
0.84
gMVP
0.78

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.

Other links and lift over

dbSNP: rs756990762; hg19: chr4-954893; API