rs1934179

Variant names:

• chrX-50439186-G-A
• rs1934179
• NM_001013742.4:c.646-14828C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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=-0.93).
• 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 rank	MANE	Protein	UniProt
DGKK	NM_001013742.4	c.646-14828C>T		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.646-14828C>T		intron_variant	Intron 1 of 27	1	NM_001013742.4	ENSP00000477515.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 49854 AN: 110234 Hom.: 9704 Cov.: 22

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

African (AFR) AF: 0.758 AC: 23007 AN: 30347

American (AMR) AF: 0.473 AC: 4911 AN: 10372

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1176 AN: 2617

East Asian (EAS) AF: 0.262 AC: 912 AN: 3480

South Asian (SAS) AF: 0.164 AC: 434 AN: 2647

European-Finnish (FIN) AF: 0.275 AC: 1609 AN: 5852

Middle Eastern (MID) AF: 0.453 AC: 97 AN: 214

European-Non Finnish (NFE) AF: 0.319 AC: 16777 AN: 52577

Other (OTH) AF: 0.456 AC: 688 AN: 1509

Alfa AF: 0.385 Hom.: 30150

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
PhyloP100		0.40

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: rs1934179; hg19: chrX-50182184;