17-56834815-C-T

Position:

• chr17-56834815-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003647.3(DGKE):​c.20C>T​(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,451,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DGKE NM_003647.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0850

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]

C17orf67 (HGNC:27900): (chromosome 17 open reading frame 67) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14994091).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKE	NM_003647.3	c.20C>T	p.Pro7Leu	missense_variant	2/12	ENST00000284061.8	NP_003638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKE	ENST00000284061.8	c.20C>T	p.Pro7Leu	missense_variant	2/12	1	NM_003647.3	ENSP00000284061	P1
DGKE	ENST00000572810.1	c.20C>T	p.Pro7Leu	missense_variant	2/2	1		ENSP00000459295
DGKE	ENST00000576869.5	n.168C>T		non_coding_transcript_exon_variant	2/6	1
C17orf67	ENST00000487705.1	n.285+3674G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1451818 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721418

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000196

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with DGKE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 7 of the DGKE protein (p.Pro7Leu). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.69	N;.
REVEL	Benign	0.057
Sift	Uncertain	0.010	D;.
Sift4G	Uncertain	0.030	D;D
Polyphen		0.10	B;.
Vest4		0.098
MutPred		0.17		Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);
MVP		0.48
MPC		0.37
ClinPred		0.68	D
GERP RS		3.7
Varity_R		0.047
gMVP		0.53

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: rs1486518180; hg19: chr17-54912176;