rs4143304

Positions:

• chrX-50403572-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001013742.4(DGKK):​c.1104G>A​(p.Leu368=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKK	NM_001013742.4	c.1104G>A	p.Leu368=	synonymous_variant	6/28	ENST00000611977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKK	ENST00000611977.2	c.1104G>A	p.Leu368=	synonymous_variant	6/28	1	NM_001013742.4	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 51181 AN: 109901 Hom.: 10509 Cov.: 22 AF XY: 0.446 AC XY: 14346 AN XY: 32197

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

GnomAD3 exomes AF: 0.383 AC: 69047 AN: 180430 Hom.: 10993 AF XY: 0.351 AC XY: 23357 AN XY: 66522

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 SAS exome AF: 0.177

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

Gnomad4 AFR exome AF: 0.809

Gnomad4 AMR exome AF: 0.569

Gnomad4 ASJ exome AF: 0.513

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.354

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

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.460

Alfa AF: 0.361 Hom.: 23826

Bravo AF: 0.506

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

LitVar

Other links and lift over

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