Variant chrX-50371729-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001013742.4(DGKK):c.3607C>T(p.Pro1203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,189,586 control chromosomes in the GnomAD database, including 3 homozygotes. There are 492 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., 58 hem., cov: 22)

Exomes 𝑓: 0.0012 ( 3 hom. 434 hem. )

Consequence

DGKK
NM_001013742.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.218

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070827007).

BP6

Variant X-50371729-G-A is Benign according to our data. Variant chrX-50371729-G-A is described in ClinVar as [Benign]. Clinvar id is 734433.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 58 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKK	NM_001013742.4 linkuse as main transcript	c.3607C>T	p.Pro1203Ser	missense_variant	26/28	ENST00000611977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKK	ENST00000611977.2 linkuse as main transcript	c.3607C>T	p.Pro1203Ser	missense_variant	26/28	1	NM_001013742.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00136

AC:

152

AN:

111507

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

AN XY:

33725

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000762

Gnomad FIN

AF:

0.0151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00111

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00214

AC:

357

AN:

166706

Hom.:

AF XY:

0.00204

AC XY:

112

AN XY:

54776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000345

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00174

Gnomad FIN exome

AF:

0.0154

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.00122

AC:

1311

AN:

1078024

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

434

AN XY:

346112

show subpopulations

Gnomad4 AFR exome

AF:

0.000115

Gnomad4 AMR exome

AF:

0.000346

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00173

Gnomad4 FIN exome

AF:

0.0157

Gnomad4 NFE exome

AF:

0.000646

Gnomad4 OTH exome

AF:

0.000904

GnomAD4 genome

AF:

0.00136

AC:

152

AN:

111562

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

AN XY:

33790

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000764

Gnomad4 FIN

AF:

0.0151

Gnomad4 NFE

AF:

0.00111

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.000434

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000304

AC:

ESP6500EA

AF:

0.000155

AC:

ExAC

AF:

0.00201

AC:

242

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 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.032

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0071

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.30

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.088

MVP

0.092

GERP RS

3.1

Varity_R

0.057

gMVP

0.11

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

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