19-3959600-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001348.3(DAPK3):​c.866G>A​(p.Gly289Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,587,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

DAPK3
NM_001348.3 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88
Variant links:
Genes affected
DAPK3 (HGNC:2676): (death associated protein kinase 3) Death-associated protein kinase 3 (DAPK3) induces morphological changes in apoptosis when overexpressed in mammalian cells. These results suggest that DAPK3 may play a role in the induction of apoptosis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06565797).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DAPK3NM_001348.3 linkuse as main transcriptc.866G>A p.Gly289Asp missense_variant 9/9 ENST00000545797.7
DAPK3NM_001375658.1 linkuse as main transcriptc.866G>A p.Gly289Asp missense_variant 9/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DAPK3ENST00000545797.7 linkuse as main transcriptc.866G>A p.Gly289Asp missense_variant 9/92 NM_001348.3 P1O43293-1
DAPK3ENST00000301264.7 linkuse as main transcriptc.866G>A p.Gly289Asp missense_variant 8/81 P1O43293-1
DAPK3ENST00000595279.1 linkuse as main transcriptn.916G>A non_coding_transcript_exon_variant 3/32
DAPK3ENST00000594894.1 linkuse as main transcript downstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152230
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000945
AC:
2
AN:
211568
Hom.:
0
AF XY:
0.00000859
AC XY:
1
AN XY:
116462
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000203
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000104
AC:
15
AN:
1435626
Hom.:
0
Cov.:
33
AF XY:
0.00000981
AC XY:
7
AN XY:
713366
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000335
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.0000343
AC:
4

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 GeneticsFeb 06, 2024The c.866G>A (p.G289D) alteration is located in exon 8 (coding exon 8) of the DAPK3 gene. This alteration results from a G to A substitution at nucleotide position 866, causing the glycine (G) at amino acid position 289 to be replaced by an aspartic acid (D). 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
0.12
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
17
DANN
Benign
0.84
DEOGEN2
Benign
0.073
T;T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.41
FATHMM_MKL
Uncertain
0.88
D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.066
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.20
N;N
MutationTaster
Benign
0.66
D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.25
N;N
REVEL
Benign
0.052
Sift
Benign
0.24
T;T
Sift4G
Benign
0.63
T;T
Polyphen
0.0
B;B
Vest4
0.066
MutPred
0.27
Loss of glycosylation at S288 (P = 0.0591);Loss of glycosylation at S288 (P = 0.0591);
MVP
0.44
MPC
0.93
ClinPred
0.037
T
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.092
gMVP
0.71

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: rs763980607; hg19: chr19-3959598; API