19-3959283-C-G

Position:

• chr19-3959283-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001348.3(DAPK3):​c.1183G>C​(p.Ala395Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: DAPK3 NM_001348.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.746

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 (HGNC:):

ACMG classification

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=0.17365825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPK3	NM_001348.3	c.1183G>C	p.Ala395Pro	missense_variant	9/9	ENST00000545797.7	NP_001339.1
DAPK3	NM_001375658.1	c.1183G>C	p.Ala395Pro	missense_variant	9/9		NP_001362587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAPK3	ENST00000545797.7	c.1183G>C	p.Ala395Pro	missense_variant	9/9	2	NM_001348.3	ENSP00000442973.1
DAPK3	ENST00000301264.7	c.1183G>C	p.Ala395Pro	missense_variant	8/8	1		ENSP00000301264.3
DAPK3	ENST00000595279.1	n.1233G>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.1183G>C (p.A395P) 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 1183, causing the alanine (A) at amino acid position 395 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	Pathogenic	0.67
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	0.067
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	0.61	D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.17	N;N
REVEL	Benign	0.20
Sift	Benign	0.087	T;T
Sift4G	Benign	0.069	T;T
Polyphen		0.83	P;P
Vest4		0.26
MutPred		0.16		Loss of MoRF binding (P = 0.056);Loss of MoRF binding (P = 0.056);
MVP		0.73
MPC		1.3
ClinPred		0.40	T
GERP RS		3.9
Varity_R		0.24
gMVP		0.48

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

Other links and lift over

dbSNP: rs2039476091; hg19: chr19-3959281;