chr4-961483-G-A

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001347.4(DGKQ):​c.2558C>T​(p.Thr853Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,602,494 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

DGKQ
NM_001347.4 missense

Scores

9
5
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.48
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DGKQNM_001347.4 linkuse as main transcriptc.2558C>T p.Thr853Met missense_variant 21/23 ENST00000273814.8 NP_001338.2
DGKQXM_047449687.1 linkuse as main transcriptc.2645C>T p.Thr882Met missense_variant 21/23 XP_047305643.1
DGKQXM_011513411.2 linkuse as main transcriptc.2558C>T p.Thr853Met missense_variant 21/23 XP_011511713.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DGKQENST00000273814.8 linkuse as main transcriptc.2558C>T p.Thr853Met missense_variant 21/231 NM_001347.4 ENSP00000273814 P1
DGKQENST00000509465.5 linkuse as main transcriptc.2360C>T p.Thr787Met missense_variant 20/225 ENSP00000425862
DGKQENST00000515182.1 linkuse as main transcriptc.203C>T p.Thr68Met missense_variant 3/55 ENSP00000421756

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152144
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000268
AC:
6
AN:
223718
Hom.:
0
AF XY:
0.0000162
AC XY:
2
AN XY:
123114
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000601
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000343
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000206
Gnomad OTH exome
AF:
0.000181
GnomAD4 exome
AF:
0.0000165
AC:
24
AN:
1450350
Hom.:
0
Cov.:
34
AF XY:
0.0000125
AC XY:
9
AN XY:
721100
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000159
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000257
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.0000200
Gnomad4 NFE exome
AF:
0.00000902
Gnomad4 OTH exome
AF:
0.0000669
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152144
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000589
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000121
ExAC
AF:
0.0000166
AC:
2

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 GeneticsJan 09, 2024The c.2558C>T (p.T853M) alteration is located in exon 21 (coding exon 21) of the DGKQ gene. This alteration results from a C to T substitution at nucleotide position 2558, causing the threonine (T) at amino acid position 853 to be replaced by a methionine (M). 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
Benign
0.25
BayesDel_addAF
Benign
-0.0059
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;.
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Pathogenic
0.45
D
MetaRNN
Uncertain
0.61
D;D
MetaSVM
Uncertain
-0.14
T
MutationAssessor
Pathogenic
3.3
M;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-5.3
D;D
REVEL
Uncertain
0.37
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0010
D;T
Polyphen
1.0
D;.
Vest4
0.80
MVP
0.74
MPC
0.59
ClinPred
0.98
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.72
gMVP
0.62

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.

Other links and lift over

dbSNP: rs759369106; hg19: chr4-955271; COSMIC: COSV53280413; COSMIC: COSV53280413; API