rs786205160

chr21-43419939-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_173354.5(SIK1):c.1039G>T(p.Glu347Ter) variant causes a stop gained change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 0)
• Consequence: SIK1 NM_173354.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.19

Genes affected

SIK1 (HGNC:11142): (salt inducible kinase 1) This gene encodes a serine/threonine protein kinase that contains a ubiquitin-associated (UBA) domain. The encoded protein is a member of the adenosine monophosphate-activated kinase (AMPK) subfamily of kinases that play a role in conserved signal transduction pathways. A mutation in this gene is associated with early infantile epileptic encephalopathy 30. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 21-43419939-C-A is Pathogenic according to our data. Variant chr21-43419939-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 190106.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIK1	NM_173354.5	c.1039G>T	p.Glu347Ter	stop_gained	9/14	ENST00000270162.8
SIK1	XM_011529474.3	c.972+295G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK1	ENST00000270162.8	c.1039G>T	p.Glu347Ter	stop_gained	9/14	1	NM_173354.5	P1
SIK1	ENST00000644871.1			upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Developmental and epileptic encephalopathy, 30 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 02, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.51
Cadd	Pathogenic	36
Dann	Uncertain	1.0
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.97	D
MutationTaster	Benign	1.0	A
Vest4		0.40
GERP RS		5.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs786205160; hg19: chr21-44839819;