13-42219343-G-T

Variant names:

• chr13-42219343-G-T
• rs180870
• NM_178009.5:c.3327G>T

Variant summary

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

The NM_178009.5(DGKH):​c.3327G>T​(p.Glu1109Asp) 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. 16/21 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: 32)
• Consequence: DGKH NM_178009.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

Genes affected

DGKH (HGNC:2854): (diacylglycerol kinase eta) This gene encodes a member of the diacylglycerol kinase (DGK) enzyme family. Members of this family are involved in regulating intracellular concentrations of diacylglycerol and phosphatidic acid. Variation in this gene has been associated with bipolar disorder. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2014]

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=0.1712257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKH	NM_178009.5	c.3327G>T	p.Glu1109Asp	missense_variant	Exon 27 of 30	ENST00000337343.9	NP_821077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.3327G>T	p.Glu1109Asp	missense_variant	Exon 27 of 30	1	NM_178009.5	ENSP00000337572.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.019	.;T;.;.;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.81	T;T;.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.29	N;N;N;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.42	.;N;N;.;N
REVEL	Benign	0.088
Sift	Benign	0.31	.;T;T;.;T
Sift4G	Benign	0.22	T;T;T;T;T
Polyphen		0.013	B;B;B;.;B
Vest4		0.13
MutPred		0.37		Loss of glycosylation at P1113 (P = 0.1724);Loss of glycosylation at P1113 (P = 0.1724);Loss of glycosylation at P1113 (P = 0.1724);.;.;
MVP		0.41
MPC		0.41
ClinPred		0.41	T
GERP RS		1.0
Varity_R		0.053
gMVP		0.11

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: rs180870; hg19: chr13-42793479;