Variant 13-42048797-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_178009.5(DGKH):c.24C>G(p.His8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000692 in 1,315,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

DGKH
NM_178009.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16022962).

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKH	NM_178009.5 linkuse as main transcript	c.24C>G	p.His8Gln	missense_variant	1/30	ENST00000337343.9	NP_821077.1	Q86XP1-1
DGKH	NM_001204504.3 linkuse as main transcript	c.24C>G	p.His8Gln	missense_variant	2/30		NP_001191433.1	Q86XP1-2A8K0I1
DGKH	NM_152910.6 linkuse as main transcript	c.24C>G	p.His8Gln	missense_variant	1/29		NP_690874.2	Q86XP1-2B4DYW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DGKH	ENST00000337343.9 linkuse as main transcript	c.24C>G	p.His8Gln	missense_variant	1/30	1	NM_178009.5	ENSP00000337572.4	Q86XP1-1
DGKH	ENST00000261491.9 linkuse as main transcript	c.24C>G	p.His8Gln	missense_variant	1/29	1		ENSP00000261491.4	Q86XP1-2
DGKH	ENST00000379274.6 linkuse as main transcript	c.24C>G	p.His8Gln	missense_variant	2/30	2		ENSP00000368576.3	Q86XP1-2
DGKH	ENST00000611224.1 linkuse as main transcript	c.-25C>G		upstream_gene_variant		2		ENSP00000482250.1	A0A087WZ02

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000705

AC:

AN:

1163618

Hom.:

Cov.:

AF XY:

0.0000642

AC XY:

AN XY:

561104

show subpopulations

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:

0.00

Gnomad4 NFE exome

AF:

0.0000802

Gnomad4 OTH exome

AF:

0.000108

GnomAD4 genome

AF:

0.0000592

AC:

AN:

151936

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.24C>G (p.H8Q) alteration is located in exon 1 (coding exon 1) of the DGKH gene. This alteration results from a C to G substitution at nucleotide position 24, causing the histidine (H) at amino acid position 8 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.012

.;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.55

T;T;.

M_CAP

Pathogenic

0.85

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

L;L;L

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.17

.;N;N

REVEL

Benign

0.26

Sift

Uncertain

0.023

.;D;D

Sift4G

Benign

0.21

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.13

MutPred

0.18

Gain of relative solvent accessibility (P = 0.0507);Gain of relative solvent accessibility (P = 0.0507);Gain of relative solvent accessibility (P = 0.0507);

MVP

0.42

MPC

0.44

ClinPred

0.30

GERP RS

2.6

Varity_R

0.16

gMVP

0.17

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over