17-56848105-A-T

Variant names:

• chr17-56848105-A-T
• rs1555599211
• NM_003647.3:c.888+40A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003647.3(DGKE):​c.888+40A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000087 in 1,148,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: DGKE NM_003647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKE	NM_003647.3	c.888+40A>T		intron_variant	Intron 5 of 11	ENST00000284061.8	NP_003638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKE	ENST00000284061.8	c.888+40A>T		intron_variant	Intron 5 of 11	1	NM_003647.3	ENSP00000284061.3
DGKE	ENST00000572944.1	c.717+40A>T		intron_variant	Intron 4 of 9	1		ENSP00000458493.1
TRIM25	ENST00000648772.1	n.*313+3838T>A		intron_variant	Intron 10 of 12			ENSP00000498158.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 8.70e-7 AC: 1 AN: 1148970 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 565850

African (AFR) AF: 0.00 AC: 0 AN: 24582

American (AMR) AF: 0.00 AC: 0 AN: 22146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17264

East Asian (EAS) AF: 0.00 AC: 0 AN: 30288

South Asian (SAS) AF: 0.0000219 AC: 1 AN: 45722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4138

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 915558

Other (OTH) AF: 0.00 AC: 0 AN: 46618

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.79
PhyloP100		0.17

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

Other links and lift over

dbSNP: rs1555599211; hg19: chr17-54925466;