dbSNP rs7647305: DGKG:n.132-10559A>G (chr3-186116501-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The ENST00000447054.5(DGKG):n.132-10559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000447054.5 is not a MANE Select or MANE Plus Clinical transcript for DGKG; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.743 (AC=113,127) in the gnomAD database across 152,174 control chromosomes, including 42,783 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.906. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.74 ( 42783 hom., cov: 32)

Consequence

DGKG
ENST00000447054.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

148 publications found

Variant links:

Genes affected

DGKG (HGNC:2853): (diacylglycerol kinase gamma) This gene encodes an enzyme that is a member of the type I subfamily of diacylglycerol kinases, which are involved in lipid metabolism. These enzymes generate phosphatidic acid by catalyzing the phosphorylation of diacylglycerol, a fundamental lipid second messenger that activates numerous proteins, including protein kinase C isoforms, Ras guanyl nucleotide-releasing proteins and some transient receptor potential channels. Diacylglycerol kinase gamma has been implicated in cell cycle regulation and in the negative regulation of macrophage differentiation in leukemia cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DGKG links:

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new If you want to explore the variant's impact on the transcript ENST00000447054.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.9058 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000447054.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKG	ENST00000447054.5	TSL:3	n.132-10559A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.744

AC:

113091

AN:

152056

Hom.:

42777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.591

Gnomad AMI

AF:

0.849

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.793

Gnomad EAS

AF:

0.928

Gnomad SAS

AF:

0.761

Gnomad FIN

AF:

0.822

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.789

Gnomad OTH

AF:

0.762

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.743

AC:

113127

AN:

152174

Hom.:

42783

Cov.:

AF XY:

0.749

AC XY:

55687

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.591

AC:

24493

AN:

41460

American (AMR)

AF:

0.811

AC:

12397

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.793

AC:

2754

AN:

3472

East Asian (EAS)

AF:

0.928

AC:

4811

AN:

5186

South Asian (SAS)

AF:

0.760

AC:

3664

AN:

4824

European-Finnish (FIN)

AF:

0.822

AC:

8710

AN:

10602

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.789

AC:

53686

AN:

68030

Other (OTH)

AF:

0.765

AC:

1615

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1478

2956

4435

5913

7391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.781

Hom.:

157479

Bravo

AF:

0.737

Asia WGS

AF:

0.842

AC:

2928

AN:

3478

Local populations

Turkish Variome

AF:

0.761

AC:

1177

AN:

1546

Hom.:

442

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.916

AC:

8208

AN:

8960

Hom.:

3753

ABraOM SABE-WGS-1171

AF:

0.772

AC:

1807

AN:

2342

Hom.:

702

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.7

(source)

DANN

Benign

0.49

PhyloP100

1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over