Genetic Variant NM_178009.5:c.3327G>C (chr13-42219343-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178009.5(DGKH):c.3327G>C(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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1109K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DGKH
NM_178009.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

19 publications found

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]

DGKH links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17498687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178009.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGKH	NM_178009.5	MANE Select	c.3327G>C	p.Glu1109Asp	missense	Exon 27 of 30	NP_821077.1	Q86XP1-1
DGKH	NM_001204504.3		c.3327G>C	p.Glu1109Asp	missense	Exon 28 of 30	NP_001191433.1	Q86XP1-2
DGKH	NM_152910.6		c.3327G>C	p.Glu1109Asp	missense	Exon 27 of 29	NP_690874.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGKH	ENST00000337343.9	TSL:1 MANE Select	c.3327G>C	p.Glu1109Asp	missense	Exon 27 of 30	ENSP00000337572.4	Q86XP1-1
DGKH	ENST00000261491.9	TSL:1	c.3327G>C	p.Glu1109Asp	missense	Exon 27 of 29	ENSP00000261491.4	Q86XP1-2
DGKH	ENST00000536612.3	TSL:1	c.2919G>C	p.Glu973Asp	missense	Exon 25 of 29	ENSP00000445114.2	Q86XP1-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461364

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726972

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111750

Other (OTH)

AF:

0.00

AC:

AN:

60372

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.019

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.81

M_CAP

Benign

0.011

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.29

PhyloP100

0.23

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.42

REVEL

Benign

0.088

Sift

Benign

0.31

Sift4G

Benign

0.22

Polyphen

0.013

Vest4

0.13

MutPred

0.37

Loss of glycosylation at P1113 (P = 0.1724)

MVP

0.42

MPC

0.41

ClinPred

0.31

GERP RS

1.0

Varity_R

0.053

gMVP

0.11

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over