chr4-961147-A-G

Position:

Variant summary

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

The NM_001347.4(DGKQ):ā€‹c.2629T>Cā€‹(p.Phe877Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000872 in 1,605,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000089 ( 0 hom. )

Consequence

DGKQ
NM_001347.4 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16
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]

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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=0.20944324).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DGKQNM_001347.4 linkuse as main transcriptc.2629T>C p.Phe877Leu missense_variant 22/23 ENST00000273814.8 NP_001338.2
DGKQXM_047449687.1 linkuse as main transcriptc.2716T>C p.Phe906Leu missense_variant 22/23 XP_047305643.1
DGKQXM_011513411.2 linkuse as main transcriptc.2629T>C p.Phe877Leu 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.2629T>C p.Phe877Leu missense_variant 22/231 NM_001347.4 ENSP00000273814 P1
DGKQENST00000509465.5 linkuse as main transcriptc.2431T>C p.Phe811Leu missense_variant 21/225 ENSP00000425862
DGKQENST00000515182.1 linkuse as main transcriptc.274T>C p.Phe92Leu missense_variant 4/55 ENSP00000421756

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152158
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD4 exome
AF:
0.00000894
AC:
13
AN:
1453458
Hom.:
0
Cov.:
34
AF XY:
0.00000691
AC XY:
5
AN XY:
723124
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:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152158
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
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
Alfa
AF:
0.0000316
Hom.:
0
Bravo
AF:
0.00000378

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 GeneticsApr 19, 2023The c.2629T>C (p.F877L) alteration is located in exon 22 (coding exon 22) of the DGKQ gene. This alteration results from a T to C substitution at nucleotide position 2629, causing the phenylalanine (F) at amino acid position 877 to be replaced by a leucine (L). 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
0.92
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.034
T;.
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.067
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.38
N;.
MutationTaster
Benign
0.89
D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-0.48
N;N
REVEL
Benign
0.14
Sift
Benign
0.12
T;T
Sift4G
Benign
0.14
T;T
Polyphen
0.33
B;.
Vest4
0.57
MutPred
0.54
Gain of glycosylation at T880 (P = 0.0281);.;
MVP
0.28
MPC
0.56
ClinPred
0.62
D
GERP RS
5.3
Varity_R
0.084
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1711852589; hg19: chr4-954935; API