X-50369028-G-GA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001013742.4(DGKK):c.3737-10_3737-9insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,182,949 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 386 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., 23 hem., cov: 22)
  • Exomes 𝑓: 0.0011 (0 hom. 363 hem.)
• Consequence: DGKK NM_001013742.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.518

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-50369028-G-GA is Benign according to our data. Variant chrX-50369028-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 725513.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKK	NM_001013742.4	c.3737-10_3737-9insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000611977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKK	ENST00000611977.2	c.3737-10_3737-9insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001013742.4	P1

Frequencies

GnomAD3 genomes AF: 0.000772 AC: 85 AN: 110055 Hom.: 0 Cov.: 22 AF XY: 0.000709 AC XY: 23 AN XY: 32455

Gnomad AFR AF: 0.000896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000483

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00158

Gnomad FIN AF: 0.000342

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000835

Gnomad OTH AF: 0.00200

GnomAD3 exomes AF: 0.000549 AC: 88 AN: 160177 Hom.: 0 AF XY: 0.000619 AC XY: 32 AN XY: 51733

Gnomad AFR exome AF: 0.00139

Gnomad AMR exome AF: 0.000244

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000129

Gnomad FIN exome AF: 0.000447

Gnomad NFE exome AF: 0.000764

Gnomad OTH exome AF: 0.000750

GnomAD4 exome AF: 0.00109 AC: 1167 AN: 1072846 Hom.: 0 Cov.: 26 AF XY: 0.00106 AC XY: 363 AN XY: 340868

Gnomad4 AFR exome AF: 0.00124

Gnomad4 AMR exome AF: 0.000351

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000193

Gnomad4 FIN exome AF: 0.000333

Gnomad4 NFE exome AF: 0.00129

Gnomad4 OTH exome AF: 0.000863

GnomAD4 genome AF: 0.000772 AC: 85 AN: 110103 Hom.: 0 Cov.: 22 AF XY: 0.000707 AC XY: 23 AN XY: 32513

Gnomad4 AFR AF: 0.000894

Gnomad4 AMR AF: 0.000483

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00159

Gnomad4 FIN AF: 0.000342

Gnomad4 NFE AF: 0.000835

Gnomad4 OTH AF: 0.00198

Bravo AF: 0.000918

Asia WGS AF: 0.000797 AC: 2 AN: 2520

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs782242724; hg19: chrX-50112027;