17-56843961-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003647.3(DGKE):c.465-58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,433,554 control chromosomes in the GnomAD database, including 382,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (38378 hom., cov: 32)
  • Exomes 𝑓: 0.73 (343824 hom.)
• Consequence: DGKE NM_003647.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.219

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-56843961-G-A is Benign according to our data. Variant chr17-56843961-G-A is described in ClinVar as [Benign]. Clinvar id is 1242093.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.465-58G>A		intron_variant		ENST00000284061.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKE	ENST00000284061.8	c.465-58G>A		intron_variant		1	NM_003647.3	P1
DGKE	ENST00000572944.1	c.295-58G>A		intron_variant		1
DGKE	ENST00000576869.5	n.613-58G>A		intron_variant, non_coding_transcript_variant		1
TRIM25	ENST00000648772.1	c.*314-171C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107324 AN: 151896 Hom.: 38373 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.722

GnomAD4 exome AF: 0.730 AC: 936136 AN: 1281540 Hom.: 343824 AF XY: 0.728 AC XY: 462435 AN XY: 635244

Gnomad4 AFR exome AF: 0.603

Gnomad4 AMR exome AF: 0.819

Gnomad4 ASJ exome AF: 0.734

Gnomad4 EAS exome AF: 0.875

Gnomad4 SAS exome AF: 0.605

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.738

Gnomad4 OTH exome AF: 0.734

GnomAD4 genome AF: 0.706 AC: 107373 AN: 152014 Hom.: 38378 Cov.: 32 AF XY: 0.708 AC XY: 52567 AN XY: 74298

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.716

Alfa AF: 0.714 Hom.: 7288

Bravo AF: 0.715

Asia WGS AF: 0.744 AC: 2586 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.3
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs3760157; hg19: chr17-54921322; COSMIC: COSV52349899; COSMIC: COSV52349899;