X-50400967-G-C

Variant names:

• chrX-50400967-G-C
• rs1934190
• NM_001013742.4:c.1411+70C>G

Variant summary

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

The NM_001013742.4(DGKK):​c.1411+70C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 991,033 control chromosomes in the GnomAD database, including 38,278 homozygotes. There are 91,102 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 0.33 (4502 hom., 10290 hem., cov: 22)
  • Exomes 𝑓: 0.32 (33776 hom. 80812 hem.)
• Consequence: DGKK NM_001013742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKK	NM_001013742.4	c.1411+70C>G		intron_variant	Intron 8 of 27	ENST00000611977.2	NP_001013764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKK	ENST00000611977.2	c.1411+70C>G		intron_variant	Intron 8 of 27	1	NM_001013742.4	ENSP00000477515.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 36197 AN: 109904 Hom.: 4503 Cov.: 22

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.425

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.322 AC: 283269 AN: 881075 Hom.: 33776 AF XY: 0.327 AC XY: 80812 AN XY: 247455

African (AFR) AF: 0.315 AC: 6781 AN: 21514

American (AMR) AF: 0.551 AC: 15186 AN: 27583

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 9003 AN: 17495

East Asian (EAS) AF: 0.291 AC: 7683 AN: 26366

South Asian (SAS) AF: 0.175 AC: 8031 AN: 45911

European-Finnish (FIN) AF: 0.300 AC: 11276 AN: 37624

Middle Eastern (MID) AF: 0.385 AC: 1291 AN: 3350

European-Non Finnish (NFE) AF: 0.319 AC: 211323 AN: 662475

Other (OTH) AF: 0.328 AC: 12695 AN: 38757

GnomAD4 genome AF: 0.329 AC: 36219 AN: 109958 Hom.: 4502 Cov.: 22 AF XY: 0.319 AC XY: 10290 AN XY: 32254

African (AFR) AF: 0.314 AC: 9482 AN: 30215

American (AMR) AF: 0.440 AC: 4526 AN: 10282

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1314 AN: 2622

East Asian (EAS) AF: 0.277 AC: 952 AN: 3432

South Asian (SAS) AF: 0.153 AC: 385 AN: 2515

European-Finnish (FIN) AF: 0.277 AC: 1604 AN: 5800

Middle Eastern (MID) AF: 0.437 AC: 93 AN: 213

European-Non Finnish (NFE) AF: 0.323 AC: 17040 AN: 52715

Other (OTH) AF: 0.352 AC: 525 AN: 1490

Alfa AF: 0.337 Hom.: 2192

Bravo AF: 0.353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.19
DANN	Benign	0.61
PhyloP100		-0.97

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: rs1934190; hg19: chrX-50143965; COSMIC: COSV65707228;