17-56844016-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS1

The NM_003647.3(DGKE):c.465-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000405 in 1,537,696 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (3 hom.)
• Consequence: DGKE NM_003647.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.01353
• Clinical Significance: Likely benign criteria provided, single submitter U:2 B:1
• Conservation: PhyloP100: 2.77

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 17-56844016-C-T is Benign according to our data. Variant chr17-56844016-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 718637.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0016 (243/152168) while in subpopulation AFR AF= 0.0045 (187/41520). AF 95% confidence interval is 0.00398. There are 0 homozygotes in gnomad4. There are 111 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKE	NM_003647.3	c.465-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000284061.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKE	ENST00000284061.8	c.465-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003647.3	P1

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 245 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00454

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00184

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000507 AC: 96 AN: 189310 Hom.: 1 AF XY: 0.000384 AC XY: 40 AN XY: 104296

Gnomad AFR exome AF: 0.00419

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000486

Gnomad NFE exome AF: 0.000245

Gnomad OTH exome AF: 0.000470

GnomAD4 exome AF: 0.000274 AC: 380 AN: 1385528 Hom.: 3 Cov.: 31 AF XY: 0.000271 AC XY: 186 AN XY: 687002

Gnomad4 AFR exome AF: 0.00456

Gnomad4 AMR exome AF: 0.00115

Gnomad4 ASJ exome AF: 0.0000417

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000135

Gnomad4 FIN exome AF: 0.0000380

Gnomad4 NFE exome AF: 0.000141

Gnomad4 OTH exome AF: 0.000874

GnomAD4 genome AF: 0.00160 AC: 243 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.00149 AC XY: 111 AN XY: 74364

Gnomad4 AFR AF: 0.00450

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000703 Hom.: 0

Bravo AF: 0.00198

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:2 Benign:1

Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 28, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	13
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.014
dbscSNV1_RF	Benign	0.038
SpliceAI score (max)		0.0		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: rs375726408; hg19: chr17-54921377;