Genetic Variant DGKZ:p.Ala39LeufsTer23 (chr11-46366365-TC-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000454345.6(DGKZ):c.114delC(p.Ala39LeufsTer23) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000146 in 1,369,666 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P38P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

DGKZ
ENST00000454345.6 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.29

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKZ	NM_001199267.2 link	c.162-921delC		intron_variant	Intron 1 of 30	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.162-921delC		intron_variant	Intron 1 of 30	1	NM_001199267.2	ENSP00000395684.2		Q13574-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1369666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

674362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31052

American (AMR)

AF:

0.00

AC:

AN:

33580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22376

East Asian (EAS)

AF:

0.00

AC:

AN:

37088

South Asian (SAS)

AF:

0.00

AC:

AN:

75436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5036

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1071602

Other (OTH)

AF:

0.00

AC:

AN:

56716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.3

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over