X-50439186-G-A

Position:

• chrX-50439186-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.646-14828C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 110,289 control chromosomes in the GnomAD database, including 9,710 homozygotes. There are 14,317 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 0.45 (9710 hom., 14317 hem., cov: 22)
• Consequence: DGKK NM_001013742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKK	NM_001013742.4	c.646-14828C>T		intron_variant		ENST00000611977.2	NP_001013764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKK	ENST00000611977.2	c.646-14828C>T		intron_variant		1	NM_001013742.4	ENSP00000477515	P1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 49854 AN: 110234 Hom.: 9704 Cov.: 22 AF XY: 0.438 AC XY: 14269 AN XY: 32586

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.457

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.453 AC: 49910 AN: 110289 Hom.: 9710 Cov.: 22 AF XY: 0.438 AC XY: 14317 AN XY: 32651

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.456

Alfa AF: 0.345 Hom.: 19879

Bravo AF: 0.489

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.25

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: rs1934179; hg19: chrX-50182184;