rs148605410
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_003647.3(DGKE):c.32C>A(p.Ser11Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,455,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic,risk factor (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
DGKE
NM_003647.3 stop_gained
NM_003647.3 stop_gained
Scores
2
2
3
Clinical Significance
Conservation
PhyloP100: 1.69
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-56834827-C-A is Pathogenic according to our data. Variant chr17-56834827-C-A is described in ClinVar as [Likely_pathogenic, risk_factor]. Clinvar id is 50789.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| DGKE | NM_003647.3 | c.32C>A | p.Ser11Ter | stop_gained | 2/12 | ENST00000284061.8 | NP_003638.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DGKE | ENST00000284061.8 | c.32C>A | p.Ser11Ter | stop_gained | 2/12 | 1 | NM_003647.3 | ENSP00000284061 | P1 | |
| DGKE | ENST00000572810.1 | c.32C>A | p.Ser11Ter | stop_gained | 2/2 | 1 | ENSP00000459295 | |||
| DGKE | ENST00000576869.5 | n.180C>A | non_coding_transcript_exon_variant | 2/6 | 1 | |||||
| C17orf67 | ENST00000487705.1 | n.285+3662G>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000412 AC: 6AN: 1455156Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 723396
GnomAD4 exome
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6
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1455156
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31
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2
AN XY:
723396
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GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely pathogenic; risk factor
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Atypical hemolytic-uremic syndrome Pathogenic:1
| Likely pathogenic, no assertion criteria provided | literature only | Richard Lifton Laboratory, Yale University School of Medicine | - | - - |
AHUS, SUSCEPTIBILITY TO, 7 Other:1
| risk factor, no assertion criteria provided | literature only | OMIM | May 01, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;D
Vest4
GERP RS
Splicing
Name
Calibrated prediction
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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