rs312262699
Variant names:
Variant summary
Our verdict is . The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
Pathogenic
The NM_003647.3(DGKE):c.486dupA(p.Val163SerfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
DGKE
NM_003647.3 frameshift
NM_003647.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.0550
Publications
2 publications found
Genes affected
DGKE (HGNC:2852): (diacylglycerol kinase epsilon) Diacylglycerol kinases are thought to be involved mainly in the regeneration of phosphatidylinositol (PI) from diacylglycerol in the PI-cycle during cell signal transduction. When expressed in mammalian cells, DGK-epsilon shows specificity for arachidonyl-containing diacylglycerol. DGK-epsilon is expressed predominantly in testis. [provided by RefSeq, Jul 2008]
TRIM25 (HGNC:12932): (tripartite motif containing 25) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein is an RNA binding protein, functions as a ubiquitin E3 ligase and is involved in multiple cellular processes, including regulation of antiviral innate immunity. [provided by RefSeq, Sep 2021]
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new If you want to explore the variant's impact on the transcript NM_003647.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-56844039-C-CA is Pathogenic according to our data. Variant chr17-56844039-C-CA is described in ClinVar as Pathogenic. ClinVar VariationId is 135639.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003647.3. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DGKE | TSL:1 MANE Select | c.486dupA | p.Val163SerfsTer3 | frameshift | Exon 3 of 12 | ENSP00000284061.3 | P52429-1 | ||
| DGKE | TSL:1 | c.315dupA | p.Val106fs | frameshift | Exon 2 of 10 | ENSP00000458493.1 | I3L112 | ||
| DGKE | TSL:1 | n.634dupA | non_coding_transcript_exon | Exon 3 of 6 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
2
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-
Atypical hemolytic-uremic syndrome (2)
-
-
-
Hemolytic uremic syndrome, atypical, susceptibility to, 7 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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Other links and lift over
dbSNP: rs312262699 ;
hg19: chr17-54921400;