chrX-50391446-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001013742.4(DGKK):​c.1835T>A​(p.Ile612Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00333 in 1,209,523 control chromosomes in the GnomAD database, including 96 homozygotes. There are 1,079 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 49 hom., 541 hem., cov: 23)
Exomes 𝑓: 0.0019 ( 47 hom. 538 hem. )

Consequence

DGKK
NM_001013742.4 missense

Scores

1
2
7

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.17
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0054518282).
BP6
Variant X-50391446-A-T is Benign according to our data. Variant chrX-50391446-A-T is described in ClinVar as [Benign]. Clinvar id is 785700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DGKKNM_001013742.4 linkuse as main transcriptc.1835T>A p.Ile612Asn missense_variant 11/28 ENST00000611977.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DGKKENST00000611977.2 linkuse as main transcriptc.1835T>A p.Ile612Asn missense_variant 11/281 NM_001013742.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0179
AC:
2001
AN:
111939
Hom.:
49
Cov.:
23
AF XY:
0.0159
AC XY:
544
AN XY:
34117
show subpopulations
Gnomad AFR
AF:
0.0624
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00587
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000373
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000150
Gnomad OTH
AF:
0.00989
GnomAD3 exomes
AF:
0.00474
AC:
857
AN:
180875
Hom.:
21
AF XY:
0.00342
AC XY:
229
AN XY:
66965
show subpopulations
Gnomad AFR exome
AF:
0.0608
Gnomad AMR exome
AF:
0.00300
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000526
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000148
Gnomad OTH exome
AF:
0.00202
GnomAD4 exome
AF:
0.00185
AC:
2034
AN:
1097530
Hom.:
47
Cov.:
30
AF XY:
0.00148
AC XY:
538
AN XY:
363168
show subpopulations
Gnomad4 AFR exome
AF:
0.0631
Gnomad4 AMR exome
AF:
0.00307
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000924
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000416
Gnomad4 OTH exome
AF:
0.00443
GnomAD4 genome
AF:
0.0178
AC:
1998
AN:
111993
Hom.:
49
Cov.:
23
AF XY:
0.0158
AC XY:
541
AN XY:
34181
show subpopulations
Gnomad4 AFR
AF:
0.0622
Gnomad4 AMR
AF:
0.00576
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000374
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000150
Gnomad4 OTH
AF:
0.00977
Alfa
AF:
0.00374
Hom.:
81
Bravo
AF:
0.0210
ESP6500AA
AF:
0.0554
AC:
196
ESP6500EA
AF:
0.000153
AC:
1
ExAC
AF:
0.00520
AC:
629

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 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
18
DANN
Benign
0.67
DEOGEN2
Benign
0.10
T
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.43
T
MetaRNN
Benign
0.0055
T
PrimateAI
Uncertain
0.60
T
Sift4G
Uncertain
0.0040
D
Polyphen
0.86
P
Vest4
0.20
MVP
0.18
GERP RS
-0.052
Varity_R
0.17
gMVP
0.90

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.

Other links and lift over

dbSNP: rs138086016; hg19: chrX-50134444; API