X-50376928-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001013742.4(DGKK):c.3112-10T>C 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 0.00433 in 1,180,503 control chromosomes in the GnomAD database, including 150 homozygotes. There are 1,327 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (65 hom., 662 hem., cov: 23)
  • Exomes 𝑓: 0.0024 (85 hom. 665 hem.)
• Consequence: DGKK NM_001013742.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.00

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant X-50376928-A-G is Benign according to our data. Variant chrX-50376928-A-G is described in ClinVar as [Benign]. Clinvar id is 780692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKK	NM_001013742.4	c.3112-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000611977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKK	ENST00000611977.2	c.3112-10T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001013742.4	P1

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 2505 AN: 111927 Hom.: 65 Cov.: 23 AF XY: 0.0192 AC XY: 655 AN XY: 34103

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00762

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000169

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.00656 AC: 1009 AN: 153924 Hom.: 24 AF XY: 0.00477 AC XY: 214 AN XY: 44832

Gnomad AFR exome AF: 0.0792

Gnomad AMR exome AF: 0.00279

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000788

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000581

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00243 AC: 2597 AN: 1068520 Hom.: 85 Cov.: 29 AF XY: 0.00196 AC XY: 665 AN XY: 338830

Gnomad4 AFR exome AF: 0.0841

Gnomad4 AMR exome AF: 0.00323

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000378

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000436

Gnomad4 OTH exome AF: 0.00544

GnomAD4 genome AF: 0.0225 AC: 2516 AN: 111983 Hom.: 65 Cov.: 23 AF XY: 0.0194 AC XY: 662 AN XY: 34169

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.00761

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000169

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0131 Hom.: 76

Bravo AF: 0.0264

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	16
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7879090; hg19: chrX-50119927;