Variant 11-46366318-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001105540.2(DGKZ):c.62A>G(p.Gln21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,573,296 control chromosomes in the GnomAD database, including 88,564 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 18461 hom., cov: 34)

Exomes 𝑓: 0.30 ( 70103 hom. )

Consequence

DGKZ
NM_001105540.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.11

Variant links:

Genes affected

DGKZ (HGNC:2857): (diacylglycerol kinase zeta) The protein encoded by this gene belongs to the eukaryotic diacylglycerol kinase family. It may attenuate protein kinase C activity by regulating diacylglycerol levels in intracellular signaling cascade and signal transduction. Alternative splicing occurs at this locus and multiple transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Nov 2010]

DGKZ links:

DGKZ (HGNC:):

DGKZ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.891087E-7).

BP6

Variant 11-46366318-A-G is Benign according to our data. Variant chr11-46366318-A-G is described in ClinVar as [Benign]. Clinvar id is 1167142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKZ	NM_001199267.2 linkuse as main transcript	c.162-973A>G		intron_variant		ENST00000456247.7	NP_001186196.1	Q13574-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKZ	ENST00000456247.7 linkuse as main transcript	c.162-973A>G		intron_variant		1	NM_001199267.2	ENSP00000395684.2		Q13574-2

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64911

AN:

152044

Hom.:

18402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.811

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.394

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.407

GnomAD3 exomes

AF:

0.301

AC:

59501

AN:

197734

Hom.:

11003

AF XY:

0.301

AC XY:

33106

AN XY:

109902

show subpopulations

Gnomad AFR exome

AF:

0.817

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.163

Gnomad SAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.161

Gnomad NFE exome

AF:

0.288

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.300

AC:

425832

AN:

1421134

Hom.:

70103

Cov.:

AF XY:

0.300

AC XY:

211583

AN XY:

705932

show subpopulations

Gnomad4 AFR exome

AF:

0.835

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.377

Gnomad4 EAS exome

AF:

0.146

Gnomad4 SAS exome

AF:

0.337

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.290

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.427

AC:

65023

AN:

152162

Hom.:

18461

Cov.:

AF XY:

0.417

AC XY:

31026

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.812

Gnomad4 AMR

AF:

0.300

Gnomad4 ASJ

AF:

0.380

Gnomad4 EAS

AF:

0.160

Gnomad4 SAS

AF:

0.333

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.407

Alfa

AF:

0.312

Hom.:

4880

Bravo

AF:

0.452

TwinsUK

AF:

0.285

AC:

1056

ALSPAC

AF:

0.300

AC:

1156

ESP6500AA

AF:

0.743

AC:

2682

ESP6500EA

AF:

0.281

AC:

2229

ExAC

AF:

0.302

AC:

35383

Asia WGS

AF:

0.302

AC:

1049

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.16

DEOGEN2

Benign

0.045

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.26

MetaRNN

Benign

8.9e-7

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.9

PrimateAI

Uncertain

0.57

PROVEAN

Benign

1.0

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.018

MPC

0.091

ClinPred

0.0027

GERP RS

4.5

Varity_R

0.055

gMVP

0.070

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