chr3-186224531-A-G

Variant names:

• chr3-186224531-A-G
• rs7620841
• NM_001346.3:c.1827-12646T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001346.3(DGKG):​c.1827-12646T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 152,258 control chromosomes in the GnomAD database, including 66,739 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 0.94 (66739 hom., cov: 31)
• Consequence: DGKG NM_001346.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 1 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKG	NM_001346.3	MANE Select	c.1827-12646T>C		intron	N/A	NP_001337.2
	DGKG	NM_001080744.2		c.1752-12646T>C		intron	N/A	NP_001074213.1
	DGKG	NM_001080745.2		c.1710-12646T>C		intron	N/A	NP_001074214.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKG	ENST00000265022.8	TSL:1 MANE Select	c.1827-12646T>C		intron	N/A	ENSP00000265022.3
	DGKG	ENST00000344484.8	TSL:1	c.1752-12646T>C		intron	N/A	ENSP00000339777.4
	DGKG	ENST00000480809.5	TSL:1	n.2090-12646T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142376 AN: 152140 Hom.: 66697 Cov.: 31

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.946

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

GnomAD4 genome AF: 0.936 AC: 142477 AN: 152258 Hom.: 66739 Cov.: 31 AF XY: 0.938 AC XY: 69824 AN XY: 74446

African (AFR) AF: 0.892 AC: 37058 AN: 41538

American (AMR) AF: 0.961 AC: 14705 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3239 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5153 AN: 5166

South Asian (SAS) AF: 0.918 AC: 4420 AN: 4814

European-Finnish (FIN) AF: 0.963 AC: 10232 AN: 10620

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.948 AC: 64512 AN: 68032

Other (OTH) AF: 0.945 AC: 2000 AN: 2116

Alfa AF: 0.933 Hom.: 32250

Bravo AF: 0.936

Asia WGS AF: 0.951 AC: 3308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.74
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7620841; hg19: chr3-185942320;