chr17-56843797-C-CAAA

Variant names:

• chr17-56843797-C-CAAA
• rs368992473
• NM_003647.3:c.465-207_465-205dupAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003647.3(DGKE):​c.465-207_465-205dupAAA 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 0.000091 (3 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 3 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.465-207_465-205dupAAA		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_465-221insAAA		intron	N/A	ENSP00000284061.3	P52429-1
	DGKE	ENST00000572944.1	TSL:1	c.294-222_294-221insAAA		intron	N/A	ENSP00000458493.1	I3L112
	DGKE	ENST00000576869.5	TSL:1	n.613-222_613-221insAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000914 AC: 10 AN: 109392 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.000138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000246

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000922

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000914 AC: 10 AN: 109392 Hom.: 3 Cov.: 0 AF XY: 0.000138 AC XY: 7 AN XY: 50750

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000138 AC: 4 AN: 29008

American (AMR) AF: 0.00 AC: 0 AN: 9698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2934

East Asian (EAS) AF: 0.00 AC: 0 AN: 3932

South Asian (SAS) AF: 0.00 AC: 0 AN: 3182

European-Finnish (FIN) AF: 0.000246 AC: 1 AN: 4070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 206

European-Non Finnish (NFE) AF: 0.0000922 AC: 5 AN: 54226

Other (OTH) AF: 0.00 AC: 0 AN: 1384

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0201086), which strongly suggests a high chance of mosaicism in these individuals.

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;