rs777106028

Variant names:

• chr21-43417676-C-A
• NM_173354.5:c.1843G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-43417676-C-A
• chr21-43417676-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173354.5(SIK1):​c.1843G>T​(p.Ala615Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000059 (1 hom.)
• Consequence: SIK1 NM_173354.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468

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=0.025228262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK1	NM_173354.5	c.1843G>T	p.Ala615Ser	missense_variant	Exon 13 of 14	ENST00000270162.8	NP_775490.2
SIK1	XM_011529474.3	c.1696G>T	p.Ala566Ser	missense_variant	Exon 12 of 13		XP_011527776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK1	ENST00000270162.8	c.1843G>T	p.Ala615Ser	missense_variant	Exon 13 of 14	1	NM_173354.5	ENSP00000270162.6

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000591 AC: 2 AN: 338508 Hom.: 1 Cov.: 0 AF XY: 0.0000119 AC XY: 2 AN XY: 167566

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000765

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.7
DANN	Benign	0.65
DEOGEN2	Benign	0.070	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.48	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.70	N
REVEL	Benign	0.088
Sift	Benign	1.0	T
Sift4G	Benign	0.93	T
Polyphen		0.0020	B
Vest4		0.045
MutPred		0.11		Gain of phosphorylation at A615 (P = 0.0889);
MVP		0.24
MPC		0.12
ClinPred		0.044	T
GERP RS		-5.4
Varity_R		0.030
gMVP		0.064

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-44837556;