rs757755073

chr21-43417001-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_173354.5(SIK1):c.2093C>T(p.Pro698Leu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: SIK1 NM_173354.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.74

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_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12588313).
• BP6: Variant 21-43417001-G-A is Benign according to our data. Variant chr21-43417001-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 476098.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIK1	NM_173354.5	c.2093C>T	p.Pro698Leu	missense_variant	14/14	ENST00000270162.8
SIK1	XM_011529474.3	c.1946C>T	p.Pro649Leu	missense_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIK1	ENST00000270162.8	c.2093C>T	p.Pro698Leu	missense_variant	14/14	1	NM_173354.5	P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ExAC AF: 0.00000959 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 30 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	13
Dann	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.68
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.14
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.035	D
Polyphen		0.0010	B
Vest4		0.16
MutPred		0.14		Loss of glycosylation at P698 (P = 0.0244);
MVP		0.19
MPC		0.44
ClinPred		0.20	T
GERP RS		2.3
Varity_R		0.082
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs757755073; hg19: chr21-44836881;