X-50454263-G-T

Variant names:

• chrX-50454263-G-T
• rs4826632
• NM_001013742.4:c.645+15771C>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.645+15771C>A 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 109,839 control chromosomes in the GnomAD database, including 9,722 homozygotes. There are 14,101 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 (9722 hom., 14101 hem., cov: 22)
• Consequence: DGKK NM_001013742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 1 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKK	NM_001013742.4	MANE Select	c.645+15771C>A		intron	N/A	NP_001013764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKK	ENST00000611977.2	TSL:1 MANE Select	c.645+15771C>A		intron	N/A	ENSP00000477515.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 49637 AN: 109784 Hom.: 9716 Cov.: 22

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.452 AC: 49691 AN: 109839 Hom.: 9722 Cov.: 22 AF XY: 0.438 AC XY: 14101 AN XY: 32203

African (AFR) AF: 0.758 AC: 22899 AN: 30200

American (AMR) AF: 0.480 AC: 4934 AN: 10285

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1158 AN: 2616

East Asian (EAS) AF: 0.247 AC: 844 AN: 3411

South Asian (SAS) AF: 0.160 AC: 410 AN: 2568

European-Finnish (FIN) AF: 0.272 AC: 1575 AN: 5781

Middle Eastern (MID) AF: 0.439 AC: 94 AN: 214

European-Non Finnish (NFE) AF: 0.320 AC: 16805 AN: 52590

Other (OTH) AF: 0.449 AC: 676 AN: 1504

Alfa AF: 0.206 Hom.: 967

Bravo AF: 0.489

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.9
DANN	Benign	0.89
PhyloP100		-0.46

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: rs4826632; hg19: chrX-50197261;