Menu
GeneBe

X-50386581-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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

2

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.32 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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
DGKKNM_001013742.4 linkuse as main transcriptc.2124C>T p.Asp708= synonymous_variant 15/28 ENST00000611977.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DGKKENST00000611977.2 linkuse as main transcriptc.2124C>T p.Asp708= synonymous_variant 15/281 NM_001013742.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0168
AC:
1874
AN:
111299
Hom.:
28
Cov.:
22
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.:
14
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.:
47
Cov.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0169
AC:
1880
AN:
111350
Hom.:
28
Cov.:
22
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 submitterclinical testingInvitaeDec 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.

Other links and lift over

dbSNP: rs5961180; hg19: chrX-50129579; API