rs4143304

Variant names:

• chrX-50403572-C-T
• rs4143304
• NM_001013742.4:c.1104G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001013742.4(DGKK):​c.1104G>A​(p.Leu368Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,205,775 control chromosomes in the GnomAD database, including 55,779 homozygotes. There are 131,076 hemizygotes in GnomAD. 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 0.47 (10518 hom., 14394 hem., cov: 22)
  • Exomes 𝑓: 0.33 (45261 hom. 116682 hem.)
• Consequence: DGKK NM_001013742.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 14 publications found

Genes affected

DGKK (HGNC:32395): (diacylglycerol kinase kappa) The protein encoded by this gene is an enzyme that phosphorylates diacylglycerol, converting it to phosphatidic acid. The encoded protein is a membrane protein and is inhibited by hydrogen peroxide. Variations in this gene have been associated with hypospadias. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=-0.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013742.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKK	NM_001013742.4	MANE Select	c.1104G>A	p.Leu368Leu	synonymous	Exon 6 of 28	NP_001013764.1	Q5KSL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKK	ENST00000611977.2	TSL:1 MANE Select	c.1104G>A	p.Leu368Leu	synonymous	Exon 6 of 28	ENSP00000477515.1	Q5KSL6
	DGKK	ENST00000924126.1		c.1104G>A	p.Leu368Leu	synonymous	Exon 6 of 27	ENSP00000594185.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 51181 AN: 109901 Hom.: 10509 Cov.: 22

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.462

GnomAD2 exomes AF: 0.383 AC: 69047 AN: 180430 AF XY: 0.351

Gnomad AFR exome AF: 0.807

Gnomad AMR exome AF: 0.577

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.258

Gnomad FIN exome AF: 0.290

Gnomad NFE exome AF: 0.327

Gnomad OTH exome AF: 0.373

GnomAD4 exome AF: 0.330 AC: 361971 AN: 1095823 Hom.: 45261 Cov.: 30 AF XY: 0.322 AC XY: 116682 AN XY: 361949

African (AFR) AF: 0.809 AC: 21337 AN: 26370

American (AMR) AF: 0.569 AC: 19999 AN: 35176

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 9937 AN: 19366

East Asian (EAS) AF: 0.260 AC: 7842 AN: 30186

South Asian (SAS) AF: 0.187 AC: 10128 AN: 54111

European-Finnish (FIN) AF: 0.297 AC: 11907 AN: 40128

Middle Eastern (MID) AF: 0.411 AC: 1700 AN: 4132

European-Non Finnish (NFE) AF: 0.313 AC: 262818 AN: 840343

Other (OTH) AF: 0.354 AC: 16303 AN: 46011

GnomAD4 genome AF: 0.466 AC: 51245 AN: 109952 Hom.: 10518 Cov.: 22 AF XY: 0.446 AC XY: 14394 AN XY: 32258

African (AFR) AF: 0.794 AC: 23831 AN: 30012

American (AMR) AF: 0.476 AC: 4943 AN: 10392

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1318 AN: 2610

East Asian (EAS) AF: 0.257 AC: 888 AN: 3459

South Asian (SAS) AF: 0.172 AC: 435 AN: 2533

European-Finnish (FIN) AF: 0.273 AC: 1585 AN: 5808

Middle Eastern (MID) AF: 0.471 AC: 99 AN: 210

European-Non Finnish (NFE) AF: 0.325 AC: 17154 AN: 52747

Other (OTH) AF: 0.460 AC: 692 AN: 1505

Alfa AF: 0.400 Hom.: 36863

Bravo AF: 0.506

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	5.4
DANN	Benign	0.78
PhyloP100		-0.22

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: rs4143304; hg19: chrX-50146570; COSMIC: COSV65706813;