dbSNP rs76583617: DGKZ:p.Thr887Arg (chr11-46379558-C-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001199267.2(DGKZ):c.2660C>G(p.Thr887Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00585 in 1,609,084 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 39 hom. )

Consequence

DGKZ
NM_001199267.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 4.07

Publications

9 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0153025985).

BP6

Variant 11-46379558-C-G is Benign according to our data. Variant chr11-46379558-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 431729.

BS2

High AC in GnomAd4 at 652 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKZ	NM_001199267.2 link	c.2660C>G	p.Thr887Arg	missense_variant	Exon 30 of 31	ENST00000456247.7	NP_001186196.1	Q13574-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKZ	ENST00000456247.7 link	c.2660C>G	p.Thr887Arg	missense_variant	Exon 30 of 31	1	NM_001199267.2	ENSP00000395684.2		Q13574-2

Frequencies

GnomAD3 genomes

AF:

0.00429

AC:

653

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00716

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00360

AC:

856

AN:

237920

AF XY:

0.00368

show subpopulations

Gnomad AFR exome

AF:

0.000941

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00472

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00158

Gnomad NFE exome

AF:

0.00618

Gnomad OTH exome

AF:

0.00380

GnomAD4 exome

AF:

0.00601

AC:

8755

AN:

1456716

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

4233

AN XY:

724452

show subpopulations

African (AFR)

AF:

0.000928

AC:

AN:

33416

American (AMR)

AF:

0.00308

AC:

136

AN:

44202

Ashkenazi Jewish (ASJ)

AF:

0.00502

AC:

130

AN:

25916

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.0000817

AC:

AN:

85650

European-Finnish (FIN)

AF:

0.00197

AC:

102

AN:

51650

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00723

AC:

8029

AN:

1110310

Other (OTH)

AF:

0.00528

AC:

318

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

411

821

1232

1642

2053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

304

608

912

1216

1520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00428

AC:

652

AN:

152368

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

289

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

41580

American (AMR)

AF:

0.00451

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00716

AC:

487

AN:

68036

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

129

161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00539

Hom.:

Bravo

AF:

0.00437

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00548

AC:

ExAC

AF:

0.00336

AC:

405

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DGKZ: BS2 -

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

atypical cerebral palsy

Uncertain:1

TIDEX, University of British Columbia

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

.;.;.;.;.;.;.;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

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

M_CAP

Benign

0.075

MetaRNN

Benign

0.015

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

0.27

.;.;.;.;.;.;.;N

PhyloP100

4.1

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-4.0

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

REVEL

Uncertain

0.57

Sift

Benign

0.20

T;D;T;T;T;T;T;T

Sift4G

Benign

0.24

T;T;T;T;T;T;T;T

Polyphen

0.20, 0.24

.;.;.;.;B;.;.;B

Vest4

0.74

MVP

0.95

MPC

1.2

ClinPred

0.044

GERP RS

4.3

Varity_R

0.50

gMVP

0.48

Mutation Taster

=87/13

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over