chr4-962457-G-A

Position:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001347.4(DGKQ):​c.2192C>T​(p.Thr731Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000759 in 1,594,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

DGKQ
NM_001347.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0700
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_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.031928033).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DGKQNM_001347.4 linkuse as main transcriptc.2192C>T p.Thr731Met missense_variant 18/23 ENST00000273814.8 NP_001338.2
DGKQXM_047449687.1 linkuse as main transcriptc.2279C>T p.Thr760Met missense_variant 18/23 XP_047305643.1
DGKQXM_011513411.2 linkuse as main transcriptc.2192C>T p.Thr731Met missense_variant 18/23 XP_011511713.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DGKQENST00000273814.8 linkuse as main transcriptc.2192C>T p.Thr731Met missense_variant 18/231 NM_001347.4 ENSP00000273814 P1
DGKQENST00000509465.5 linkuse as main transcriptc.1994C>T p.Thr665Met missense_variant 17/225 ENSP00000425862
DGKQENST00000515182.1 linkuse as main transcript upstream_gene_variant 5 ENSP00000421756

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152214
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000762
AC:
17
AN:
223070
Hom.:
0
AF XY:
0.0000740
AC XY:
9
AN XY:
121582
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000917
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000352
Gnomad FIN exome
AF:
0.000144
Gnomad NFE exome
AF:
0.000108
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000784
AC:
113
AN:
1441842
Hom.:
0
Cov.:
32
AF XY:
0.0000754
AC XY:
54
AN XY:
716526
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000139
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000119
Gnomad4 FIN exome
AF:
0.0000903
Gnomad4 NFE exome
AF:
0.0000904
Gnomad4 OTH exome
AF:
0.0000334
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152332
Hom.:
0
Cov.:
34
AF XY:
0.0000537
AC XY:
4
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000483
Hom.:
0
Bravo
AF:
0.0000718
ExAC
AF:
0.0000910
AC:
11

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 GeneticsJul 11, 2022The c.2192C>T (p.T731M) alteration is located in exon 18 (coding exon 18) of the DGKQ gene. This alteration results from a C to T substitution at nucleotide position 2192, causing the threonine (T) at amino acid position 731 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
0.066
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
6.5
DANN
Benign
0.94
DEOGEN2
Benign
0.031
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.032
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.83
N
REVEL
Benign
0.044
Sift
Benign
0.046
D
Sift4G
Benign
0.081
T
Polyphen
0.65
P
Vest4
0.097
MVP
0.19
MPC
0.13
ClinPred
0.032
T
GERP RS
-2.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.012
gMVP
0.26

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: rs528009075; hg19: chr4-956245; COSMIC: COSV53276986; COSMIC: COSV53276986; API