Variant chr19-3959330-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001348.3(DAPK3):c.1136G>C(p.Arg379Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,591,532 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

DAPK3
NM_001348.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82

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]

DAPK3 links:

DAPK3 (HGNC:):

DAPK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27231804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPK3	NM_001348.3 linkuse as main transcript	c.1136G>C	p.Arg379Pro	missense_variant	9/9	ENST00000545797.7	NP_001339.1	O43293-1B3KNJ3
DAPK3	NM_001375658.1 linkuse as main transcript	c.1136G>C	p.Arg379Pro	missense_variant	9/9		NP_001362587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DAPK3	ENST00000545797.7 linkuse as main transcript	c.1136G>C	p.Arg379Pro	missense_variant	9/9	2	NM_001348.3	ENSP00000442973.1	O43293-1
DAPK3	ENST00000301264.7 linkuse as main transcript	c.1136G>C	p.Arg379Pro	missense_variant	8/8	1		ENSP00000301264.3	O43293-1
DAPK3	ENST00000595279.1 linkuse as main transcript	n.1186G>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152190

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000158

AC:

AN:

215004

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

118814

show subpopulations

Gnomad AFR exome

AF:

0.0000744

Gnomad AMR exome

AF:

0.0000610

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000935

Gnomad NFE exome

AF:

0.000307

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000163

AC:

234

AN:

1439342

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

108

AN XY:

716168

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000686

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000779

Gnomad4 NFE exome

AF:

0.000193

Gnomad4 OTH exome

AF:

0.000217

GnomAD4 genome

AF:

0.000171

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000390

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000351

AC:

ExAC

AF:

0.000175

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.1136G>C (p.R379P) alteration is located in exon 8 (coding exon 8) of the DAPK3 gene. This alteration results from a G to C substitution at nucleotide position 1136, causing the arginine (R) at amino acid position 379 to be replaced by a proline (P). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.74

.;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

0.71

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.20

Sift

Benign

0.15

T;T

Sift4G

Uncertain

0.057

T;T

Polyphen

0.79

P;P

Vest4

0.53

MVP

0.75

MPC

1.2

ClinPred

0.067

GERP RS

4.9

Varity_R

0.56

gMVP

0.66

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