NM_003647.3:c.486dupA

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

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

Scores

Not classified

Clinical Significance

Likely pathogenic; risk factor no assertion criteria provided P:1O:1

Conservation

PhyloP100: -0.0550

Publications

2 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: 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 CliVar as Pathogenic. Clinvar id is 135639.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-56844039-C-CA is described in CliVar as Pathogenic. Clinvar id is 135639.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-56844039-C-CA is described in CliVar as Pathogenic. Clinvar id is 135639.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-56844039-C-CA is described in CliVar as Pathogenic. Clinvar id is 135639.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-56844039-C-CA is described in CliVar as Pathogenic. Clinvar id is 135639.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-56844039-C-CA is described in CliVar as Pathogenic. Clinvar id is 135639.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DGKENM_003647.3 linkc.486dupA p.Val163SerfsTer3 frameshift_variant Exon 3 of 12 ENST00000284061.8 NP_003638.1 P52429-1A1L4Q0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DGKEENST00000284061.8 linkc.486dupA p.Val163SerfsTer3 frameshift_variant Exon 3 of 12 1 NM_003647.3 ENSP00000284061.3 P52429-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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
-
Richard Lifton Laboratory, Yale University School of Medicine
Significance:Likely pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only

- -

Hemolytic uremic syndrome, atypical, susceptibility to, 7 Other:1
May 01, 2013
OMIM
Significance:risk factor
Review Status:no assertion criteria provided
Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.055
Mutation Taster
=0/200
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs312262699; hg19: chr17-54921400; API