rs3760158

chr17-56844133-A-Cchr17-56844133-A-Gchr17-56844133-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003647.3(DGKE):c.579A>C(p.Thr193=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.356

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]

ACMG classification

Verdict is Benign. Variant got -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. Variant chr17-56844133-A-C is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
DGKE	NM_003647.3	c.579A>C	p.Thr193=	synonymous_variant	3/12	ENST00000284061.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKE	ENST00000284061.8	c.579A>C	p.Thr193=	synonymous_variant	3/12	1	NM_003647.3	P1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107508 AN: 151854 Hom.: 38486 Cov.: 31

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

GnomAD3 exomes AF: 0.726 AC: 156530 AN: 215610 Hom.: 57668 AF XY: 0.721 AC XY: 84669 AN XY: 117456

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 SAS exome AF: 0.597

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.: 31 AF XY: 0.728 AC XY: 513891 AN XY: 705420

Gnomad4 AFR exome AF: 0.610

Gnomad4 AMR exome AF: 0.818

Gnomad4 ASJ exome AF: 0.736

Gnomad4 EAS exome AF: 0.879

Gnomad4 SAS exome AF: 0.607

Gnomad4 FIN exome AF: 0.677

Gnomad4 NFE exome AF: 0.738

Gnomad4 OTH exome AF: 0.734

GnomAD4 genome AF: 0.708 AC: 107564 AN: 151972 Hom.: 38496 Cov.: 31 AF XY: 0.709 AC XY: 52618 AN XY: 74214

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.717

Alfa AF: 0.726 Hom.: 47393

Bravo AF: 0.717

Asia WGS AF: 0.746 AC: 2592 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 08, 2021	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Immunoglobulin-mediated membranoproliferative glomerulonephritis Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.1
Dann	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs3760158; hg19: chr17-54921494; COSMIC: COSV52349906;