17-56844133-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003647.3(DGKE):c.579A>C(p.Thr193Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 1,570,546 control chromosomes in the GnomAD database, including 419,981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T193T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.71 ( 38496 hom., cov: 31)

Exomes 𝑓: 0.73 ( 381485 hom. )

Consequence

DGKE
NM_003647.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.356

Publications

22 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]

DGKE links:

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]

TRIM25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-56844133-A-C is Benign according to our data. Variant chr17-56844133-A-C is described in ClinVar as [Benign]. Clinvar id is 259116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.356 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKE	NM_003647.3 link	c.579A>C	p.Thr193Thr	synonymous_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
DGKE	ENST00000284061.8 link	c.579A>C	p.Thr193Thr	synonymous_variant	Exon 3 of 12	1	NM_003647.3	ENSP00000284061.3		P52429-1

Frequencies

GnomAD3 genomes

AF:

0.708

AC:

107508

AN:

151854

Hom.:

38486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.618

Gnomad AMI

AF:

0.730

Gnomad AMR

AF:

0.799

Gnomad ASJ

AF:

0.730

Gnomad EAS

AF:

0.910

Gnomad SAS

AF:

0.607

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.735

Gnomad OTH

AF:

0.723

GnomAD2 exomes

AF:

0.726

AC:

156530

AN:

215610

AF XY:

0.721

show subpopulations

Gnomad AFR exome

AF:

0.604

Gnomad AMR exome

AF:

0.824

Gnomad ASJ exome

AF:

0.739

Gnomad EAS exome

AF:

0.919

Gnomad FIN exome

AF:

0.682

Gnomad NFE exome

AF:

0.728

Gnomad OTH exome

AF:

0.733

GnomAD4 exome

AF:

0.731

AC:

1037347

AN:

1418574

Hom.:

381485

Cov.:

AF XY:

0.728

AC XY:

513891

AN XY:

705420

show subpopulations

African (AFR)

AF:

0.610

AC:

18709

AN:

30652

American (AMR)

AF:

0.818

AC:

28626

AN:

34974

Ashkenazi Jewish (ASJ)

AF:

0.736

AC:

18480

AN:

25102

East Asian (EAS)

AF:

0.879

AC:

32915

AN:

37448

South Asian (SAS)

AF:

0.607

AC:

47908

AN:

78984

European-Finnish (FIN)

AF:

0.677

AC:

35870

AN:

52994

Middle Eastern (MID)

AF:

0.746

AC:

4216

AN:

5652

European-Non Finnish (NFE)

AF:

0.738

AC:

807536

AN:

1094090

Other (OTH)

AF:

0.734

AC:

43087

AN:

58678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

12236

24472

36707

48943

61179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.708

AC:

107564

AN:

151972

Hom.:

38496

Cov.:

AF XY:

0.709

AC XY:

52618

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.618

AC:

25599

AN:

41424

American (AMR)

AF:

0.799

AC:

12206

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.730

AC:

2533

AN:

3470

East Asian (EAS)

AF:

0.910

AC:

4713

AN:

5180

South Asian (SAS)

AF:

0.605

AC:

2914

AN:

4814

European-Finnish (FIN)

AF:

0.686

AC:

7223

AN:

10532

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.735

AC:

49974

AN:

67962

Other (OTH)

AF:

0.717

AC:

1511

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1582

3165

4747

6330

7912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.726

Hom.:

55836

Bravo

AF:

0.717

Asia WGS

AF:

0.746

AC:

2592

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 08, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Immunoglobulin-mediated membranoproliferative glomerulonephritis

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.1

(source)

DANN

Benign

0.59

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

17-56844133-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over