Variant 11-46366356-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting

The NM_001105540.2(DGKZ):c.100C>T(p.Arg34Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,531,268 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 3 hom. )

Consequence

DGKZ
NM_001105540.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.551

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009575248).

BP6

Variant 11-46366356-C-T is Benign according to our data. Variant chr11-46366356-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2169469.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 23 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKZ	NM_001199267.2 linkuse as main transcript	c.162-935C>T		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.162-935C>T		intron_variant		1	NM_001199267.2	ENSP00000395684.2		Q13574-2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000456

AC:

AN:

140258

Hom.:

AF XY:

0.000586

AC XY:

AN XY:

76750

show subpopulations

Gnomad AFR exome

AF:

0.000114

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000792

Gnomad SAS exome

AF:

0.00305

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000326

Gnomad OTH exome

AF:

0.000534

GnomAD4 exome

AF:

0.000221

AC:

305

AN:

1378970

Hom.:

Cov.:

AF XY:

0.000276

AC XY:

188

AN XY:

680108

show subpopulations

Gnomad4 AFR exome

AF:

0.0000638

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000442

Gnomad4 EAS exome

AF:

0.000399

Gnomad4 SAS exome

AF:

0.00256

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000659

Gnomad4 OTH exome

AF:

0.000350

GnomAD4 genome

AF:

0.000151

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00310

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000251

AC:

ExAC

AF:

0.000391

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Benign

0.13

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.42

MVP

0.77

MPC

0.24

ClinPred

0.094

GERP RS

3.6

Varity_R

0.19

gMVP

0.41

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