17-56864155-C-T

Variant names:

• chr17-56864155-C-T
• rs1992554
• NM_003647.3:c.*1364C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003647.3(DGKE):​c.*1364C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,096 control chromosomes in the GnomAD database, including 38,527 homozygotes. 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: 𝑓 0.71 (38527 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DGKE NM_003647.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432
• Publications: 8 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]

LOC124904037 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKE	NM_003647.3	c.*1364C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000284061.8	NP_003638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKE	ENST00000284061.8	c.*1364C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_003647.3	ENSP00000284061.3
DGKE	ENST00000572944.1	c.*1889C>T		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000458493.1
TRIM25	ENST00000648772.1	n.1364-9045G>A		intron_variant	Intron 8 of 12			ENSP00000498158.1
TRIM25	ENST00000682766.1	n.1364-9045G>A		intron_variant	Intron 8 of 9			ENSP00000507876.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107604 AN: 151978 Hom.: 38517 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.722

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.708 AC: 107660 AN: 152096 Hom.: 38527 Cov.: 32 AF XY: 0.709 AC XY: 52745 AN XY: 74368

African (AFR) AF: 0.618 AC: 25639 AN: 41462

American (AMR) AF: 0.799 AC: 12209 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2533 AN: 3470

East Asian (EAS) AF: 0.911 AC: 4713 AN: 5174

South Asian (SAS) AF: 0.606 AC: 2920 AN: 4818

European-Finnish (FIN) AF: 0.686 AC: 7249 AN: 10562

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49990 AN: 68004

Other (OTH) AF: 0.716 AC: 1512 AN: 2112

Alfa AF: 0.714 Hom.: 18451

Bravo AF: 0.717

Asia WGS AF: 0.748 AC: 2602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.94
DANN	Benign	0.43
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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: rs1992554; hg19: chr17-54941516;