rs751294210

Positions:

• chr21-43417602-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_173354.5(SIK1):​c.1917C>T​(p.Gly639=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 1)
  • Exomes 𝑓: 0.0000091 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIK1 NM_173354.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.26

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 21-43417602-G-A is Benign according to our data. Variant chr21-43417602-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 542721.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.26 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIK1	NM_173354.5	c.1917C>T	p.Gly639=	synonymous_variant	13/14	ENST00000270162.8	NP_775490.2
SIK1	XM_011529474.3	c.1770C>T	p.Gly590=	synonymous_variant	12/13		XP_011527776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIK1	ENST00000270162.8	c.1917C>T	p.Gly639=	synonymous_variant	13/14	1	NM_173354.5	ENSP00000270162	P1

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD3 exomes AF: 0.0000451 AC: 6 AN: 132986 Hom.: 0 AF XY: 0.0000535 AC XY: 4 AN XY: 74708

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000645

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000106

Gnomad SAS exome AF: 0.0000781

Gnomad FIN exome AF: 0.000123

Gnomad NFE exome AF: 0.0000153

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000908 AC: 2 AN: 220198 Hom.: 0 Cov.: 0 AF XY: 0.00000916 AC XY: 1 AN XY: 109124

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: 0.000241

Gnomad4 NFE exome AF: 0.00000593

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.63

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: rs751294210; hg19: chr21-44837482; COSMIC: COSV99532364; COSMIC: COSV99532364;