rs1344286

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178009.5(DGKH):​c.193A>C​(p.Thr65Pro) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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, splice_region

Scores

2
6
11
Splicing: ADA: 0.3135
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.31
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.22653326).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DGKHNM_178009.5 linkuse as main transcriptc.193A>C p.Thr65Pro missense_variant, splice_region_variant 2/30 ENST00000337343.9
DGKHNM_001204504.3 linkuse as main transcriptc.193A>C p.Thr65Pro missense_variant, splice_region_variant 3/30
DGKHNM_152910.6 linkuse as main transcriptc.193A>C p.Thr65Pro missense_variant, splice_region_variant 2/29

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DGKHENST00000337343.9 linkuse as main transcriptc.193A>C p.Thr65Pro missense_variant, splice_region_variant 2/301 NM_178009.5 P1Q86XP1-1
DGKHENST00000261491.9 linkuse as main transcriptc.193A>C p.Thr65Pro missense_variant, splice_region_variant 2/291 Q86XP1-2
DGKHENST00000379274.6 linkuse as main transcriptc.193A>C p.Thr65Pro missense_variant, splice_region_variant 3/302 Q86XP1-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Uncertain
0.084
D
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.040
.;T;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D;D;.
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.23
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
M;M;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-1.3
.;N;N
REVEL
Benign
0.18
Sift
Benign
0.082
.;T;T
Sift4G
Benign
0.24
T;T;T
Polyphen
1.0
D;B;D
Vest4
0.52
MutPred
0.27
Loss of phosphorylation at T65 (P = 0.0308);Loss of phosphorylation at T65 (P = 0.0308);Loss of phosphorylation at T65 (P = 0.0308);
MVP
0.49
MPC
1.3
ClinPred
0.97
D
GERP RS
5.5
Varity_R
0.42
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.31
dbscSNV1_RF
Benign
0.55
SpliceAI score (max)
0.14
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1344286; hg19: chr13-42701599; API