Variant 7-14701685-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001350709.2(DGKB):c.512G>A(p.Ser171Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,456,628 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

DGKB
NM_001350709.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKB	NM_001350709.2 linkuse as main transcript	c.512G>A	p.Ser171Asn	missense_variant	7/26	ENST00000402815.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKB	ENST00000402815.6 linkuse as main transcript	c.512G>A	p.Ser171Asn	missense_variant	7/26	5	NM_001350709.2	P4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248404

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134788

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1456628

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724950

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:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000828

AC:

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

Apr 08, 2022

The c.512G>A (p.S171N) alteration is located in exon 6 (coding exon 6) of the DGKB gene. This alteration results from a G to A substitution at nucleotide position 512, causing the serine (S) at amino acid position 171 to be replaced by an asparagine (N). 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

0.15

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.28

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;.;.;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

D;.;D;D;D

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.51

D;D;D;D;D

MetaSVM

Uncertain

-0.043

MutationAssessor

Benign

1.7

L;L;.;.;L

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.9

N;N;N;N;N

REVEL

Uncertain

0.40

Sift

Uncertain

0.011

D;D;D;D;D

Sift4G

Uncertain

0.013

D;D;D;D;D

Polyphen

1.0

D;D;.;.;P

Vest4

0.65

MutPred

0.62

Loss of disorder (P = 0.1);Loss of disorder (P = 0.1);Loss of disorder (P = 0.1);.;Loss of disorder (P = 0.1);

MVP

0.73

MPC

0.39

ClinPred

0.80

GERP RS

6.0

Varity_R

0.47

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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