chr17-56848105-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_003647.3(DGKE):​c.888+40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000174 in 1,148,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

DGKE
NM_003647.3 intron

Scores

2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.171

Publications

4 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 17-56848105-A-G is Pathogenic according to our data. Variant chr17-56848105-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 548648.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DGKENM_003647.3 linkc.888+40A>G intron_variant Intron 5 of 11 ENST00000284061.8 NP_003638.1 P52429-1A1L4Q0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DGKEENST00000284061.8 linkc.888+40A>G intron_variant Intron 5 of 11 1 NM_003647.3 ENSP00000284061.3 P52429-1
DGKEENST00000572944.1 linkc.717+40A>G intron_variant Intron 4 of 9 1 ENSP00000458493.1 I3L112
TRIM25ENST00000648772.1 linkn.*313+3838T>C intron_variant Intron 10 of 12 ENSP00000498158.1 A0A3B3IUA7

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.00000174
AC:
2
AN:
1148968
Hom.:
0
Cov.:
16
AF XY:
0.00000177
AC XY:
1
AN XY:
565848
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
24582
American (AMR)
AF:
0.00
AC:
0
AN:
22146
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
17264
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30288
South Asian (SAS)
AF:
0.00
AC:
0
AN:
45722
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
42654
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4138
European-Non Finnish (NFE)
AF:
0.00000218
AC:
2
AN:
915556
Other (OTH)
AF:
0.00
AC:
0
AN:
46618
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Hemolytic-uremic syndrome Pathogenic:1
Apr 08, 2015
Yale Center for Mendelian Genomics, Yale University
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
21
DANN
Benign
0.82
PhyloP100
0.17
Mutation Taster
=35/65
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.98
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.98
Position offset: -1
DS_DL_spliceai
0.68
Position offset: -40

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1555599211; hg19: chr17-54925466; API