X-50388583-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001013742.4(DGKK):c.1962C>T(p.Thr654=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,205,755 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 81 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000081 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.00020 (0 hom. 80 hem.)
• Consequence: DGKK NM_001013742.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.867

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant X-50388583-G-A is Benign according to our data. Variant chrX-50388583-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 750755.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.867 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKK	NM_001013742.4	c.1962C>T	p.Thr654=	synonymous_variant	13/28	ENST00000611977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKK	ENST00000611977.2	c.1962C>T	p.Thr654=	synonymous_variant	13/28	1	NM_001013742.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000812 AC: 9 AN: 110847 Hom.: 0 Cov.: 23 AF XY: 0.0000302 AC XY: 1 AN XY: 33089

Gnomad AFR AF: 0.0000329

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000151

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000741 AC: 13 AN: 175464 Hom.: 0 AF XY: 0.0000483 AC XY: 3 AN XY: 62088

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000166

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000203 AC: 222 AN: 1094908 Hom.: 0 Cov.: 29 AF XY: 0.000222 AC XY: 80 AN XY: 360712

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000996

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000248

Gnomad4 OTH exome AF: 0.000239

GnomAD4 genome AF: 0.0000812 AC: 9 AN: 110847 Hom.: 0 Cov.: 23 AF XY: 0.0000302 AC XY: 1 AN XY: 33089

Gnomad4 AFR AF: 0.0000329

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000151

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000117

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

Jun 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	5.9
Dann	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs367649149; hg19: chrX-50131581;