chrX-50450910-A-G

Variant names:

• chrX-50450910-A-G
• rs1934176
• NM_001013742.4:c.645+19124T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001013742.4(DGKK):​c.645+19124T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 110,339 control chromosomes in the GnomAD database, including 9,746 homozygotes. There are 14,233 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 (9746 hom., 14233 hem., cov: 22)
• Consequence: DGKK NM_001013742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 2 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=-0.89).
• 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 rank	MANE	Protein	UniProt
DGKK	NM_001013742.4	c.645+19124T>C		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.645+19124T>C		intron_variant	Intron 1 of 27	1	NM_001013742.4	ENSP00000477515.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 49836 AN: 110284 Hom.: 9740 Cov.: 22

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.452 AC: 49892 AN: 110339 Hom.: 9746 Cov.: 22 AF XY: 0.436 AC XY: 14233 AN XY: 32681

African (AFR) AF: 0.758 AC: 22951 AN: 30283

American (AMR) AF: 0.477 AC: 4945 AN: 10376

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1172 AN: 2617

East Asian (EAS) AF: 0.261 AC: 894 AN: 3428

South Asian (SAS) AF: 0.157 AC: 408 AN: 2595

European-Finnish (FIN) AF: 0.274 AC: 1625 AN: 5931

Middle Eastern (MID) AF: 0.451 AC: 96 AN: 213

European-Non Finnish (NFE) AF: 0.319 AC: 16822 AN: 52720

Other (OTH) AF: 0.452 AC: 680 AN: 1505

Alfa AF: 0.406 Hom.: 7737

Bravo AF: 0.490

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.80
PhyloP100		-0.20

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: rs1934176; hg19: chrX-50193908;