X-50425307-G-C

Variant names:

• chrX-50425307-G-C
• rs9969978
• NM_001013742.4:c.646-949C>G

Variant summary

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

The NM_001013742.4(DGKK):​c.646-949C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 109,718 control chromosomes in the GnomAD database, including 4,566 homozygotes. There are 10,321 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 (4566 hom., 10321 hem., cov: 22)
• Consequence: DGKK NM_001013742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKK	NM_001013742.4	c.646-949C>G		intron_variant	Intron 1 of 27	ENST00000611977.2	NP_001013764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKK	ENST00000611977.2	c.646-949C>G		intron_variant	Intron 1 of 27	1	NM_001013742.4	ENSP00000477515.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 36394 AN: 109671 Hom.: 4568 Cov.: 22 AF XY: 0.321 AC XY: 10306 AN XY: 32063

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.332 AC: 36410 AN: 109718 Hom.: 4566 Cov.: 22 AF XY: 0.321 AC XY: 10321 AN XY: 32120

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.349

Alfa AF: 0.319 Hom.: 2001

Bravo AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.71

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: rs9969978; hg19: chrX-50168305;