rs200315286

Variant names:

• chr21-43421003-G-A
• rs200315286
• NM_173354.5:c.748+7C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-43421003-G-A
• chr21-43421003-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_173354.5(SIK1):​c.748+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: SIK1 NM_173354.5 splice_region, intron
• Scores: Splicing: ADA: 0.00004800
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.363
• Publications: 0 publications found

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]

SIK1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 30

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• early myoclonic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• generalized epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 21-43421003-G-A is Benign according to our data. Variant chr21-43421003-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 542714.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK1	NM_173354.5	c.748+7C>T		splice_region_variant, intron_variant	Intron 7 of 13	ENST00000270162.8	NP_775490.2
SIK1	XM_011529474.3	c.748+7C>T		splice_region_variant, intron_variant	Intron 7 of 12		XP_011527776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK1	ENST00000270162.8	c.748+7C>T		splice_region_variant, intron_variant	Intron 7 of 13	1	NM_173354.5	ENSP00000270162.6
SIK1	ENST00000644689.1	n.550+7C>T		splice_region_variant, intron_variant	Intron 4 of 4
SIK1	ENST00000478426.1	n.*109C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.000205 AC: 50 AN: 244378 AF XY: 0.000219

Gnomad AFR exome AF: 0.0000639

Gnomad AMR exome AF: 0.000643

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000191

Gnomad OTH exome AF: 0.000508

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.000197 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 30 Benign:1

Dec 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.1
DANN	Benign	0.71
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000048
dbscSNV1_RF	Benign	0.024
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: rs200315286; hg19: chr21-44840883;