9-87605066-G-C

Variant names:

• chr9-87605066-G-C
• rs1330227143
• NM_004938.4:c.175G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004938.4(DAPK1):​c.175G>C​(p.Glu59Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DAPK1 NM_004938.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.93
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.175G>C	p.Glu59Gln	missense	Exon 3 of 26	NP_004929.2	P53355-1
	DAPK1	NM_001288729.2		c.175G>C	p.Glu59Gln	missense	Exon 3 of 26	NP_001275658.1	P53355-1
	DAPK1	NM_001288730.2		c.175G>C	p.Glu59Gln	missense	Exon 3 of 26	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.175G>C	p.Glu59Gln	missense	Exon 3 of 26	ENSP00000386135.3	P53355-1
	DAPK1	ENST00000358077.9	TSL:1	c.175G>C	p.Glu59Gln	missense	Exon 3 of 26	ENSP00000350785.5	P53355-1
	DAPK1	ENST00000472284.5	TSL:1	c.175G>C	p.Glu59Gln	missense	Exon 3 of 26	ENSP00000417076.1	P53355-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.4	L
PhyloP100		9.9
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.24
Sift	Benign	0.29	T
Sift4G	Benign	0.50	T
Polyphen		0.95	P
Vest4		0.65
MutPred		0.37		Gain of MoRF binding (P = 0.0338)
MVP		0.62
MPC		0.60
ClinPred		0.75	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.53
Mutation Taster		=42/58	disease causing

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: rs1330227143; hg19: chr9-90219981;