Variant 19-3959231-C-A 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.1235G>T(p.Arg412Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,898 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DAPK3
NM_001348.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

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:

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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=0.28312474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPK3	NM_001348.3 linkuse as main transcript	c.1235G>T	p.Arg412Leu	missense_variant	9/9	ENST00000545797.7	NP_001339.1	O43293-1B3KNJ3
DAPK3	NM_001375658.1 linkuse as main transcript	c.1235G>T	p.Arg412Leu	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.1235G>T	p.Arg412Leu	missense_variant	9/9	2	NM_001348.3	ENSP00000442973.1	O43293-1
DAPK3	ENST00000301264.7 linkuse as main transcript	c.1235G>T	p.Arg412Leu	missense_variant	8/8	1		ENSP00000301264.3	O43293-1
DAPK3	ENST00000595279.1 linkuse as main transcript	n.1285G>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1447898

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720480

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Mar 31, 2023

The c.1235G>T (p.R412L) alteration is located in exon 8 (coding exon 8) of the DAPK3 gene. This alteration results from a G to T substitution at nucleotide position 1235, causing the arginine (R) at amino acid position 412 to be replaced by a leucine (L). 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

0.21

BayesDel_addAF

Benign

0.0022

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.047

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

.;D

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

0.93

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.28

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.80

P;P

Vest4

0.39

MutPred

0.18

Loss of solvent accessibility (P = 0.0606);Loss of solvent accessibility (P = 0.0606);

MVP

0.71

MPC

1.2

ClinPred

0.80

GERP RS

3.9

Varity_R

0.25

gMVP

0.39

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