19-3958399-A-G

Variant names:

• chr19-3958399-A-G
• rs7255123
• ENST00000723280.1:n.1768-2239A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000723280.1(ENSG00000294388):​n.1768-2239A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 456,038 control chromosomes in the GnomAD database, including 143,812 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (47440 hom., cov: 34)
  • Exomes 𝑓: 0.79 (96372 hom.)
• Consequence: ENSG00000294388 ENST00000723280.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 13 publications found

Genes affected

ENSG00000294388 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPK3	NM_001348.3	c.*702T>C		downstream_gene_variant		ENST00000545797.7	NP_001339.1
DAPK3	NM_001375658.1	c.*702T>C		downstream_gene_variant			NP_001362587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000294388	ENST00000723280.1	n.1768-2239A>G		intron_variant	Intron 1 of 1
DAPK3	ENST00000545797.7	c.*702T>C		downstream_gene_variant		2	NM_001348.3	ENSP00000442973.1
DAPK3	ENST00000301264.7	c.*702T>C		downstream_gene_variant		1		ENSP00000301264.3
DAPK3	ENST00000595279.1	n.*59T>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119760 AN: 152100 Hom.: 47399 Cov.: 34

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.781

GnomAD4 exome AF: 0.794 AC: 241171 AN: 303820 Hom.: 96372 AF XY: 0.791 AC XY: 136836 AN XY: 172998

African (AFR) AF: 0.742 AC: 6400 AN: 8628

American (AMR) AF: 0.890 AC: 24248 AN: 27260

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 7900 AN: 10762

East Asian (EAS) AF: 0.966 AC: 8892 AN: 9208

South Asian (SAS) AF: 0.770 AC: 46021 AN: 59744

European-Finnish (FIN) AF: 0.789 AC: 9758 AN: 12360

Middle Eastern (MID) AF: 0.768 AC: 2135 AN: 2780

European-Non Finnish (NFE) AF: 0.784 AC: 124535 AN: 158856

Other (OTH) AF: 0.793 AC: 11282 AN: 14222

GnomAD4 genome AF: 0.787 AC: 119859 AN: 152218 Hom.: 47440 Cov.: 34 AF XY: 0.792 AC XY: 58935 AN XY: 74430

African (AFR) AF: 0.749 AC: 31095 AN: 41526

American (AMR) AF: 0.856 AC: 13092 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2505 AN: 3472

East Asian (EAS) AF: 0.963 AC: 4984 AN: 5176

South Asian (SAS) AF: 0.770 AC: 3723 AN: 4832

European-Finnish (FIN) AF: 0.804 AC: 8533 AN: 10616

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53352 AN: 67994

Other (OTH) AF: 0.782 AC: 1649 AN: 2110

Alfa AF: 0.783 Hom.: 75207

Bravo AF: 0.789

Asia WGS AF: 0.865 AC: 3005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.67
PhyloP100		-1.1
Mutation Taster		=98/2	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7255123; hg19: chr19-3958397;