X-50387546-G-A

Position:

• chrX-50387546-G-A

Variant summary

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

The NM_001013742.4(DGKK):​c.2118+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,182,573 control chromosomes in the GnomAD database, including 26,745 homozygotes. There are 89,746 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (3324 hom., 8727 hem., cov: 23)
  • Exomes 𝑓: 0.24 (23421 hom. 81019 hem.)
• Consequence: DGKK NM_001013742.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKK	NM_001013742.4	c.2118+8C>T		splice_region_variant, intron_variant		ENST00000611977.2	NP_001013764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKK	ENST00000611977.2	c.2118+8C>T		splice_region_variant, intron_variant		1	NM_001013742.4	ENSP00000477515.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 30476 AN: 111003 Hom.: 3325 Cov.: 23 AF XY: 0.262 AC XY: 8717 AN XY: 33265

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.290

GnomAD3 exomes AF: 0.263 AC: 45445 AN: 172595 Hom.: 5242 AF XY: 0.236 AC XY: 14050 AN XY: 59465

Gnomad AFR exome AF: 0.342

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.396

Gnomad EAS exome AF: 0.0896

Gnomad SAS exome AF: 0.131

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.246

Gnomad OTH exome AF: 0.278

GnomAD4 exome AF: 0.243 AC: 260025 AN: 1071514 Hom.: 23421 Cov.: 24 AF XY: 0.237 AC XY: 81019 AN XY: 342188

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.449

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.275 AC: 30486 AN: 111059 Hom.: 3324 Cov.: 23 AF XY: 0.262 AC XY: 8727 AN XY: 33331

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.0896

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.289

Alfa AF: 0.262 Hom.: 19422

Bravo AF: 0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.4
DANN	Benign	0.57

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: rs7883609; hg19: chrX-50130544;