U.S. flag

An official website of the United States government

NM_001163435.3(TBCK):c.1897+1G>A AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 25, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002516437.2

Allele description [Variation Report for NM_001163435.3(TBCK):c.1897+1G>A]

NM_001163435.3(TBCK):c.1897+1G>A

Gene:
TBCK:TBC1 domain containing kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q24
Genomic location:
Preferred name:
NM_001163435.3(TBCK):c.1897+1G>A
HGVS:
  • NC_000004.12:g.106194717C>T
  • NG_034057.3:g.126967G>A
  • NM_001163435.3:c.1897+1G>AMANE SELECT
  • NM_001163436.4:c.1897+1G>A
  • NM_001163437.3:c.1780+1G>A
  • NM_001290768.2:c.1381+1G>A
  • NM_033115.5:c.1708+1G>A
  • LRG_836t1:c.1897+1G>A
  • LRG_836:g.126967G>A
  • NC_000004.11:g.107115874C>T
  • NG_034057.2:g.131779G>A
  • NM_001163435.1:c.1897+1G>A
  • NM_001163435.2:c.[1897+1G>A]
  • NM_033115.4:c.1708+1G>A
Nucleotide change:
1897+1G-A
Links:
OMIM: 616899.0001; dbSNP: rs374319146
NCBI 1000 Genomes Browser:
rs374319146
Molecular consequence:
  • NM_001163435.3:c.1897+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001163436.4:c.1897+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001163437.3:c.1780+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001290768.2:c.1381+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_033115.5:c.1708+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003525523Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 25, 2024) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy.

Chong JX, Caputo V, Phelps IG, Stella L, Worgan L, Dempsey JC, Nguyen A, Leuzzi V, Webster R, Pizzuti A, Marvin CT, Ishak GE, Ardern-Holmes S, Richmond Z; University of Washington Center for Mendelian Genomics., Bamshad MJ, Ortiz-Gonzalez XR, Tartaglia M, Chopra M, Doherty D.

Am J Hum Genet. 2016 Apr 7;98(4):772-81. doi: 10.1016/j.ajhg.2016.01.016. Epub 2016 Mar 31.

PubMed [citation]
PMID:
27040692
PMCID:
PMC4833196
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV003525523.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change affects a donor splice site in intron 21 of the TBCK gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TBCK are known to be pathogenic (PMID: 27040692, 30103036). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individual(s) with TBCK-related conditions (PMID: 25558065). This variant is also known as c.1708+1G>A. ClinVar contains an entry for this variant (Variation ID: 183338). Studies have shown that disruption of this splice site alters TBCK gene expression (PMID: 27040691). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 6, 2024