X-50380968-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013742.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKK	NM_001013742.4	MANE Select	c.2658-891C>A		intron	N/A	NP_001013764.1	Q5KSL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKK	ENST00000611977.2	TSL:1 MANE Select	c.2658-891C>A		intron	N/A	ENSP00000477515.1	Q5KSL6
	DGKK	ENST00000924126.1		c.2658-891C>A		intron	N/A	ENSP00000594185.1

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 7037 AN: 111520 Hom.: 211 Cov.: 23

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

African (AFR) AF: 0.0112 AC: 345 AN: 30796

American (AMR) AF: 0.0910 AC: 958 AN: 10524

Ashkenazi Jewish (ASJ) AF: 0.0924 AC: 244 AN: 2640

East Asian (EAS) AF: 0.177 AC: 622 AN: 3510

South Asian (SAS) AF: 0.0707 AC: 185 AN: 2617

European-Finnish (FIN) AF: 0.0835 AC: 498 AN: 5966

Middle Eastern (MID) AF: 0.0596 AC: 13 AN: 218

European-Non Finnish (NFE) AF: 0.0759 AC: 4030 AN: 53108

Other (OTH) AF: 0.0807 AC: 122 AN: 1511

Alfa AF: 0.0684 Hom.: 3576

Bravo AF: 0.0627

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.60
PhyloP100		0.47

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

Other links and lift over

dbSNP: rs4599945; hg19: chrX-50123966;