12-55940655-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001345.5(DGKA):ā€‹c.950A>Gā€‹(p.His317Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 1,596,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

DGKA
NM_001345.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.783
Variant links:
Genes affected
DGKA (HGNC:2849): (diacylglycerol kinase alpha) The protein encoded by this gene belongs to the eukaryotic diacylglycerol kinase family. It acts as a modulator that competes with protein kinase C for the second messenger diacylglycerol in intracellular signaling pathways. It also plays an important role in the resynthesis of phosphatidylinositols and phosphorylating diacylglycerol to phosphatidic acid. Several transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Apr 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.091713846).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DGKANM_001345.5 linkuse as main transcriptc.950A>G p.His317Arg missense_variant 12/24 ENST00000331886.10 NP_001336.2 P23743-1A0A024RB23

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DGKAENST00000331886.10 linkuse as main transcriptc.950A>G p.His317Arg missense_variant 12/245 NM_001345.5 ENSP00000328405.5 P23743-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000843
AC:
2
AN:
237228
Hom.:
0
AF XY:
0.00000777
AC XY:
1
AN XY:
128668
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000569
Gnomad SAS exome
AF:
0.0000350
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000208
AC:
3
AN:
1444558
Hom.:
0
Cov.:
32
AF XY:
0.00000418
AC XY:
3
AN XY:
718146
show subpopulations
Gnomad4 AFR exome
AF:
0.0000310
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.05e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 29, 2024The c.950A>G (p.H317R) alteration is located in exon 12 (coding exon 11) of the DGKA gene. This alteration results from a A to G substitution at nucleotide position 950, causing the histidine (H) at amino acid position 317 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
17
DANN
Benign
0.89
DEOGEN2
Benign
0.25
T;.;T;T
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.41
.;T;T;.
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.092
T;T;T;T
MetaSVM
Benign
-0.63
T
MutationAssessor
Benign
0.55
N;.;N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
0.040
N;N;N;N
REVEL
Uncertain
0.30
Sift
Benign
0.074
T;T;T;T
Sift4G
Benign
0.45
T;T;T;T
Polyphen
0.0
B;B;B;B
Vest4
0.19
MutPred
0.48
Gain of catalytic residue at L312 (P = 0);.;Gain of catalytic residue at L312 (P = 0);Gain of catalytic residue at L312 (P = 0);
MVP
0.61
MPC
0.73
ClinPred
0.030
T
GERP RS
-2.1
Varity_R
0.043
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs765249382; hg19: chr12-56334439; API