chr17-56843797-C-CAAAA

Variant names:

• chr17-56843797-C-CAAAA
• rs368992473
• NM_003647.3:c.465-208_465-205dupAAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_003647.3(DGKE):​c.465-208_465-205dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0021 (12 hom., cov: 0)
• Consequence: DGKE NM_003647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• 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]

LOC124904036 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00212 (232/109384) while in subpopulation AMR AF = 0.00381 (37/9702). AF 95% confidence interval is 0.00299. There are 12 homozygotes in GnomAd4. There are 115 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003647.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKE	NM_003647.3	MANE Select	c.465-208_465-205dupAAAA		intron	N/A	NP_003638.1	A1L4Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKE	ENST00000284061.8	TSL:1 MANE Select	c.465-222_465-221insAAAA		intron	N/A	ENSP00000284061.3	P52429-1
	DGKE	ENST00000572944.1	TSL:1	c.294-222_294-221insAAAA		intron	N/A	ENSP00000458493.1	I3L112
	DGKE	ENST00000576869.5	TSL:1	n.613-222_613-221insAAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00213 AC: 233 AN: 109384 Hom.: 12 Cov.: 0

Gnomad AFR AF: 0.00359

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00382

Gnomad ASJ AF: 0.000341

Gnomad EAS AF: 0.00102

Gnomad SAS AF: 0.00220

Gnomad FIN AF: 0.00319

Gnomad MID AF: 0.00485

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.00217

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00212 AC: 232 AN: 109384 Hom.: 12 Cov.: 0 AF XY: 0.00227 AC XY: 115 AN XY: 50766

African (AFR) AF: 0.00355 AC: 103 AN: 29046

American (AMR) AF: 0.00381 AC: 37 AN: 9702

Ashkenazi Jewish (ASJ) AF: 0.000341 AC: 1 AN: 2934

East Asian (EAS) AF: 0.00102 AC: 4 AN: 3920

South Asian (SAS) AF: 0.00222 AC: 7 AN: 3156

European-Finnish (FIN) AF: 0.00319 AC: 13 AN: 4070

Middle Eastern (MID) AF: 0.00510 AC: 1 AN: 196

European-Non Finnish (NFE) AF: 0.00116 AC: 63 AN: 54216

Other (OTH) AF: 0.00216 AC: 3 AN: 1392

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.031
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs368992473; hg19: chr17-54921158;