NM_001013742.4:c.943-2063C>T

Variant names:

• chrX-50406247-G-A
• rs1934188
• NM_001013742.4:c.943-2063C>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.943-2063C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 110,837 control chromosomes in the GnomAD database, including 3,774 homozygotes. There are 9,715 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 0.30 (3774 hom., 9715 hem., cov: 23)
• Consequence: DGKK NM_001013742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKK	NM_001013742.4	c.943-2063C>T		intron_variant	Intron 4 of 27	ENST00000611977.2	NP_001013764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKK	ENST00000611977.2	c.943-2063C>T		intron_variant	Intron 4 of 27	1	NM_001013742.4	ENSP00000477515.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 33194 AN: 110782 Hom.: 3775 Cov.: 23

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.388

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.300 AC: 33209 AN: 110837 Hom.: 3774 Cov.: 23 AF XY: 0.294 AC XY: 9715 AN XY: 33073

African (AFR) AF: 0.243 AC: 7415 AN: 30536

American (AMR) AF: 0.416 AC: 4335 AN: 10417

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1262 AN: 2628

East Asian (EAS) AF: 0.260 AC: 905 AN: 3483

South Asian (SAS) AF: 0.151 AC: 397 AN: 2625

European-Finnish (FIN) AF: 0.271 AC: 1606 AN: 5935

Middle Eastern (MID) AF: 0.389 AC: 79 AN: 203

European-Non Finnish (NFE) AF: 0.311 AC: 16420 AN: 52831

Other (OTH) AF: 0.331 AC: 498 AN: 1506

Alfa AF: 0.325 Hom.: 23064

Bravo AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.34
DANN	Benign	0.80
PhyloP100		-0.89

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: rs1934188; hg19: chrX-50149245;