9-87578076-C-T

Variant names:

• chr9-87578076-C-T
• rs4878104
• NM_004938.4:c.63-26878C>T

Variant summary

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

The NM_004938.4(DAPK1):​c.63-26878C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,860 control chromosomes in the GnomAD database, including 13,094 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 0.41 (13094 hom., cov: 31)
• Consequence: DAPK1 NM_004938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 27 publications found

Genes affected

DAPK1 (HGNC:2674): (death associated protein kinase 1) Death-associated protein kinase 1 is a positive mediator of gamma-interferon induced programmed cell death. DAPK1 encodes a structurally unique 160-kD calmodulin dependent serine-threonine kinase that carries 8 ankyrin repeats and 2 putative P-loop consensus sites. It is a tumor suppressor candidate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

DAPK1 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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 = 0.72 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004938.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAPK1	NM_004938.4	MANE Select	c.63-26878C>T		intron	N/A	NP_004929.2	P53355-1
	DAPK1	NM_001288729.2		c.63-26878C>T		intron	N/A	NP_001275658.1	P53355-1
	DAPK1	NM_001288730.2		c.63-26878C>T		intron	N/A	NP_001275659.1	P53355-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAPK1	ENST00000408954.8	TSL:2 MANE Select	c.63-26878C>T		intron	N/A	ENSP00000386135.3	P53355-1
	DAPK1	ENST00000358077.9	TSL:1	c.63-26878C>T		intron	N/A	ENSP00000350785.5	P53355-1
	DAPK1	ENST00000472284.5	TSL:1	c.63-26878C>T		intron	N/A	ENSP00000417076.1	P53355-1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61596 AN: 151742 Hom.: 13081 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.442

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.406 AC: 61643 AN: 151860 Hom.: 13094 Cov.: 31 AF XY: 0.414 AC XY: 30709 AN XY: 74228

African (AFR) AF: 0.414 AC: 17127 AN: 41386

American (AMR) AF: 0.438 AC: 6678 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1564 AN: 3466

East Asian (EAS) AF: 0.740 AC: 3818 AN: 5160

South Asian (SAS) AF: 0.577 AC: 2772 AN: 4804

European-Finnish (FIN) AF: 0.379 AC: 3996 AN: 10546

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24307 AN: 67928

Other (OTH) AF: 0.448 AC: 944 AN: 2108

Alfa AF: 0.381 Hom.: 21279

Bravo AF: 0.410

Asia WGS AF: 0.617 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.81
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4878104; hg19: chr9-90192991;