X-50400967-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001013742.4(DGKK):c.1411+70C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 991,033 control chromosomes in the GnomAD database, including 38,278 homozygotes. There are 91,102 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 0.33 (4502 hom., 10290 hem., cov: 22)
  • Exomes 𝑓: 0.32 (33776 hom. 80812 hem.)
• Consequence: DGKK NM_001013742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKK	NM_001013742.4	c.1411+70C>G		intron_variant		ENST00000611977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKK	ENST00000611977.2	c.1411+70C>G		intron_variant		1	NM_001013742.4	P1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 36197 AN: 109904 Hom.: 4503 Cov.: 22 AF XY: 0.319 AC XY: 10273 AN XY: 32192

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.425

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.322 AC: 283269 AN: 881075 Hom.: 33776 AF XY: 0.327 AC XY: 80812 AN XY: 247455

Gnomad4 AFR exome AF: 0.315

Gnomad4 AMR exome AF: 0.551

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.329 AC: 36219 AN: 109958 Hom.: 4502 Cov.: 22 AF XY: 0.319 AC XY: 10290 AN XY: 32254

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.352

Alfa AF: 0.337 Hom.: 2192

Bravo AF: 0.353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.19
Dann	Benign	0.61

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: rs1934190; hg19: chrX-50143965; COSMIC: COSV65707228;