Genetic Variant DGKZ:n.1469T>C (chr11-46377988-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000527211.5(DGKZ):n.1469T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 625,016 control chromosomes in the GnomAD database, including 11,855 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4776 hom., cov: 33)

Exomes 𝑓: 0.16 ( 7079 hom. )

Consequence

DGKZ
ENST00000527211.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.389

Publications

7 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000527211.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DGKZ	NM_001199267.2	MANE Select	c.2340-210T>C	intron	N/A	NP_001186196.1
DGKZ	NM_001105540.2		c.2907-210T>C	intron	N/A	NP_001099010.1
DGKZ	NM_201532.3		c.2391-210T>C	intron	N/A	NP_963290.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DGKZ	ENST00000527211.5	TSL:1	n.1469T>C	non_coding_transcript_exon	Exon 1 of 3
DGKZ	ENST00000456247.7	TSL:1 MANE Select	c.2340-210T>C	intron	N/A	ENSP00000395684.2
DGKZ	ENST00000454345.6	TSL:1	c.2907-210T>C	intron	N/A	ENSP00000412178.1

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34013

AN:

152108

Hom.:

4755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.0654

Gnomad SAS

AF:

0.152

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.210

GnomAD4 exome

AF:

0.162

AC:

76662

AN:

472790

Hom.:

7079

Cov.:

AF XY:

0.161

AC XY:

40183

AN XY:

249242

show subpopulations

African (AFR)

AF:

0.394

AC:

5132

AN:

13022

American (AMR)

AF:

0.103

AC:

2246

AN:

21818

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

2553

AN:

14388

East Asian (EAS)

AF:

0.0623

AC:

1922

AN:

30864

South Asian (SAS)

AF:

0.158

AC:

7553

AN:

47882

European-Finnish (FIN)

AF:

0.126

AC:

3714

AN:

29558

Middle Eastern (MID)

AF:

0.214

AC:

516

AN:

2416

European-Non Finnish (NFE)

AF:

0.168

AC:

48185

AN:

286000

Other (OTH)

AF:

0.180

AC:

4841

AN:

26842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3116

6232

9348

12464

15580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.224

AC:

34066

AN:

152226

Hom.:

4776

Cov.:

AF XY:

0.218

AC XY:

16250

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.398

AC:

16490

AN:

41482

American (AMR)

AF:

0.140

AC:

2138

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

619

AN:

3472

East Asian (EAS)

AF:

0.0651

AC:

338

AN:

5190

South Asian (SAS)

AF:

0.151

AC:

730

AN:

4830

European-Finnish (FIN)

AF:

0.120

AC:

1279

AN:

10616

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.172

AC:

11719

AN:

68016

Other (OTH)

AF:

0.206

AC:

436

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1326

2651

3977

5302

6628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.142

Hom.:

386

Bravo

AF:

0.232

Asia WGS

AF:

0.122

AC:

426

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.2

(source)

DANN

Benign

0.62

PhyloP100

0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over