Variant 7-14718665-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001350709.2(DGKB):c.343G>A(p.Ala115Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DGKB
NM_001350709.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

Variant links:

Genes affected

DGKB (HGNC:2850): (diacylglycerol kinase beta) Diacylglycerol kinases (DGKs) are regulators of the intracellular concentration of the second messenger diacylglycerol (DAG) and thus play a key role in cellular processes. Nine mammalian isotypes have been identified, which are encoded by separate genes. Mammalian DGK isozymes contain a conserved catalytic (kinase) domain and a cysteine-rich domain (CRD). The protein encoded by this gene is a diacylglycerol kinase, beta isotype. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

DGKB links:

DGKB (HGNC:):

DGKB links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05781269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKB	NM_001350709.2 linkuse as main transcript	c.343G>A	p.Ala115Thr	missense_variant	6/26	ENST00000402815.6	NP_001337638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000402815.6 linkuse as main transcript	c.343G>A	p.Ala115Thr	missense_variant	6/26	5	NM_001350709.2	ENSP00000384909.1		B5MBY2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456280

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724380

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Mar 20, 2024

The c.343G>A (p.A115T) alteration is located in exon 5 (coding exon 5) of the DGKB gene. This alteration results from a G to A substitution at nucleotide position 343, causing the alanine (A) at amino acid position 115 to be replaced by a threonine (T). 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

0.062

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.043

T;T;.;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.84

T;.;T;T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.058

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;N;.;.;N

MutationTaster

Benign

0.98

N;N;N;N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.16

N;N;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.37

T;T;T;T;T

Sift4G

Benign

0.58

T;T;T;T;T

Polyphen

0.0

B;B;.;.;B

Vest4

0.034

MutPred

0.27

Gain of glycosylation at A115 (P = 0.0029);Gain of glycosylation at A115 (P = 0.0029);Gain of glycosylation at A115 (P = 0.0029);.;Gain of glycosylation at A115 (P = 0.0029);

MVP

0.17

MPC

0.29

ClinPred

0.19

GERP RS

3.3

Varity_R

0.034

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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