X-50380968-G-T

Variant names:

• chrX-50380968-G-T
• rs4599945
• NM_001013742.4:c.2658-891C>A

Variant summary

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

The NM_001013742.4(DGKK):​c.2658-891C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 111,572 control chromosomes in the GnomAD database, including 210 homozygotes. There are 2,093 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 0.063 (210 hom., 2093 hem., cov: 23)
• Consequence: DGKK NM_001013742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKK	NM_001013742.4	c.2658-891C>A		intron_variant	Intron 18 of 27	ENST00000611977.2	NP_001013764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKK	ENST00000611977.2	c.2658-891C>A		intron_variant	Intron 18 of 27	1	NM_001013742.4	ENSP00000477515.1

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 7037 AN: 111520 Hom.: 211 Cov.: 23 AF XY: 0.0621 AC XY: 2093 AN XY: 33718

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.0924

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0701

Gnomad FIN AF: 0.0835

Gnomad MID AF: 0.0586

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.0824

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

GnomAD4 genome AF: 0.0631 AC: 7035 AN: 111572 Hom.: 210 Cov.: 23 AF XY: 0.0620 AC XY: 2093 AN XY: 33780

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.0910

Gnomad4 ASJ AF: 0.0924

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.0707

Gnomad4 FIN AF: 0.0835

Gnomad4 NFE AF: 0.0759

Gnomad4 OTH AF: 0.0807

Alfa AF: 0.0685 Hom.: 2587

Bravo AF: 0.0627

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.60

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: rs4599945; hg19: chrX-50123966;