17-56834827-C-G

Variant names:

• chr17-56834827-C-G
• rs148605410
• NM_003647.3:c.32C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_003647.3(DGKE):​c.32C>G​(p.Ser11Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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: 33)
• Consequence: DGKE NM_003647.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 5 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]

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 0.59049 (below the threshold of 3.09). Trascript score misZ: 0.87515 (below the threshold of 3.09). GenCC associations: The gene is linked to immunoglobulin-mediated membranoproliferative glomerulonephritis, atypical hemolytic-uremic syndrome with DGKE deficiency.
• BP4: Computational evidence support a benign effect (MetaRNN=0.12849176).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKE	NM_003647.3	MANE Select	c.32C>G	p.Ser11Trp	missense	Exon 2 of 12	NP_003638.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKE	ENST00000284061.8	TSL:1 MANE Select	c.32C>G	p.Ser11Trp	missense	Exon 2 of 12	ENSP00000284061.3
	DGKE	ENST00000572810.1	TSL:1	c.32C>G	p.Ser11Trp	missense	Exon 2 of 2	ENSP00000459295.1
	DGKE	ENST00000576869.5	TSL:1	n.180C>G		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.088	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.070
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.021	D
Polyphen		0.56	P
Vest4		0.39
MVP		0.55
MPC		0.86
ClinPred		0.43	T
GERP RS		2.3
PromoterAI		0.037	Neutral
Varity_R		0.15
gMVP		0.51

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: rs148605410; hg19: chr17-54912188;