Variant X-50386581-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001013742.4(DGKK):c.2124C>T(p.Asp708=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 1,204,126 control chromosomes in the GnomAD database, including 75 homozygotes. There are 1,882 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 28 hom., 474 hem., cov: 22)

Exomes 𝑓: 0.0043 ( 47 hom. 1408 hem. )

Consequence

DGKK
NM_001013742.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.320

Variant links:

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]

DGKK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant X-50386581-G-A is Benign according to our data. Variant chrX-50386581-G-A is described in ClinVar as [Benign]. Clinvar id is 781550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.32 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKK	NM_001013742.4 linkuse as main transcript	c.2124C>T	p.Asp708=	synonymous_variant	15/28	ENST00000611977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKK	ENST00000611977.2 linkuse as main transcript	c.2124C>T	p.Asp708=	synonymous_variant	15/28	1	NM_001013742.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0168

AC:

1874

AN:

111299

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

467

AN XY:

33505

show subpopulations

Gnomad AFR

AF:

0.0515

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00690

Gnomad ASJ

AF:

0.00798

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000380

Gnomad FIN

AF:

0.000332

Gnomad MID

AF:

0.00840

Gnomad NFE

AF:

0.00341

Gnomad OTH

AF:

0.0146

GnomAD3 exomes

AF:

0.00600

AC:

1066

AN:

177554

Hom.:

AF XY:

0.00485

AC XY:

311

AN XY:

64080

show subpopulations

Gnomad AFR exome

AF:

0.0547

Gnomad AMR exome

AF:

0.00329

Gnomad ASJ exome

AF:

0.00487

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000758

Gnomad FIN exome

AF:

0.0000656

Gnomad NFE exome

AF:

0.00294

Gnomad OTH exome

AF:

0.00525

GnomAD4 exome

AF:

0.00426

AC:

4660

AN:

1092776

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

1408

AN XY:

358608

show subpopulations

Gnomad4 AFR exome

AF:

0.0550

Gnomad4 AMR exome

AF:

0.00373

Gnomad4 ASJ exome

AF:

0.00508

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000763

Gnomad4 FIN exome

AF:

0.000200

Gnomad4 NFE exome

AF:

0.00310

Gnomad4 OTH exome

AF:

0.00645

GnomAD4 genome

AF:

0.0169

AC:

1880

AN:

111350

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

474

AN XY:

33566

show subpopulations

Gnomad4 AFR

AF:

0.0516

Gnomad4 AMR

AF:

0.00689

Gnomad4 ASJ

AF:

0.00798

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000381

Gnomad4 FIN

AF:

0.000332

Gnomad4 NFE

AF:

0.00341

Gnomad4 OTH

AF:

0.0144

Alfa

AF:

0.0108

Hom.:

108

Bravo

AF:

0.0190

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.1

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over