chr4-961475-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001347.4(DGKQ):c.2566G>A(p.Val856Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,598,178 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00023 ( 7 hom. )
Consequence
DGKQ
NM_001347.4 missense
NM_001347.4 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: -0.152
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 Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0079835355).
BP6
Variant 4-961475-C-T is Benign according to our data. Variant chr4-961475-C-T is described in ClinVar as [Benign]. Clinvar id is 3052604.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DGKQ | NM_001347.4 | c.2566G>A | p.Val856Met | missense_variant | 21/23 | ENST00000273814.8 | NP_001338.2 | |
DGKQ | XM_047449687.1 | c.2653G>A | p.Val885Met | missense_variant | 21/23 | XP_047305643.1 | ||
DGKQ | XM_011513411.2 | c.2566G>A | p.Val856Met | missense_variant | 21/23 | XP_011511713.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DGKQ | ENST00000273814.8 | c.2566G>A | p.Val856Met | missense_variant | 21/23 | 1 | NM_001347.4 | ENSP00000273814 | P1 | |
DGKQ | ENST00000509465.5 | c.2368G>A | p.Val790Met | missense_variant | 20/22 | 5 | ENSP00000425862 | |||
DGKQ | ENST00000515182.1 | c.211G>A | p.Val71Met | missense_variant | 3/5 | 5 | ENSP00000421756 |
Frequencies
GnomAD3 genomes AF: 0.000302 AC: 46AN: 152122Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00118 AC: 254AN: 216102Hom.: 3 AF XY: 0.000831 AC XY: 99AN XY: 119116
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GnomAD4 exome AF: 0.000228 AC: 329AN: 1445940Hom.: 7 Cov.: 33 AF XY: 0.000191 AC XY: 137AN XY: 718620
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GnomAD4 genome AF: 0.000296 AC: 45AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21AN XY: 74426
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
DGKQ-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 21, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Loss of catalytic residue at V856 (P = 0.0056);.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at