NM_004938.4:c.63-1651T>C

Variant names:

• chr9-87603303-T-C
• rs3124237
• NM_004938.4:c.63-1651T>C

Variant summary

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

The NM_004938.4(DAPK1):​c.63-1651T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,126 control chromosomes in the GnomAD database, including 2,830 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 0.16 (2830 hom., cov: 32)
• Consequence: DAPK1 NM_004938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPK1	NM_004938.4	c.63-1651T>C		intron_variant	Intron 2 of 25	ENST00000408954.8	NP_004929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAPK1	ENST00000408954.8	c.63-1651T>C		intron_variant	Intron 2 of 25	2	NM_004938.4	ENSP00000386135.3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24761 AN: 152008 Hom.: 2819 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.163 AC: 24808 AN: 152126 Hom.: 2830 Cov.: 32 AF XY: 0.161 AC XY: 11993 AN XY: 74384

African (AFR) AF: 0.324 AC: 13421 AN: 41458

American (AMR) AF: 0.0954 AC: 1459 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 699 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.112 AC: 541 AN: 4822

European-Finnish (FIN) AF: 0.130 AC: 1381 AN: 10602

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6881 AN: 67984

Other (OTH) AF: 0.139 AC: 294 AN: 2108

Alfa AF: 0.122 Hom.: 2416

Bravo AF: 0.166

Asia WGS AF: 0.0790 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.76
PhyloP100		-0.17
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: rs3124237; hg19: chr9-90218218;