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NM_013432.5(TONSL):c.866-1G>C AND Sponastrime dysplasia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 24, 2019
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000790532.1

Allele description [Variation Report for NM_013432.5(TONSL):c.866-1G>C]

NM_013432.5(TONSL):c.866-1G>C

Gene:
TONSL:tonsoku like, DNA repair protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q24.3
Genomic location:
Preferred name:
NM_013432.5(TONSL):c.866-1G>C
HGVS:
  • NC_000008.11:g.144441112C>G
  • NM_013432.5:c.866-1G>CMANE SELECT
  • NC_000008.10:g.145666495C>G
  • NM_013432.4:c.866-1G>C
Nucleotide change:
IVS7, G-C, -1
Links:
OMIM: 604546.0008; dbSNP: rs1424148372
NCBI 1000 Genomes Browser:
rs1424148372
Molecular consequence:
  • NM_013432.5:c.866-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Sponastrime dysplasia
Synonyms:
SPONDYLAR AND NASAL ALTERATIONS WITH STRIATED METAPHYSES
Identifiers:
MONDO: MONDO:0010068; MedGen: C1300260; OMIM: 271510

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000929864OMIM
no assertion criteria provided
Pathogenic
(Jul 24, 2019) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Bi-allelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes.

Burrage LC, Reynolds JJ, Baratang NV, Phillips JB, Wegner J, McFarquhar A, Higgs MR, Christiansen AE, Lanza DG, Seavitt JR, Jain M, Li X, Parry DA, Raman V, Chitayat D, Chinn IK, Bertuch AA, Karaviti L, Schlesinger AE, Earl D, Bamshad M, Savarirayan R, et al.

Am J Hum Genet. 2019 Mar 7;104(3):422-438. doi: 10.1016/j.ajhg.2019.01.007. Epub 2019 Feb 14.

PubMed [citation]
PMID:
30773277
PMCID:
PMC6408318

Details of each submission

From OMIM, SCV000929864.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a sister and brother (family 7) with the sponastrime type of spondyloepimetaphyseal dysplasia (SEMDSP; 271510), Burrage et al. (2019) identified compound heterozygosity for a splicing mutation (c.866-1G-C, NM_013432.4) in intron 7 of the TONSL gene, and a c.595G-A transition in exon 6, resulting in a glu199-to-lys (E199K) substitution. The mutations segregated with disease in the family and neither was found in the gnomAD database. Functional studies in a fibroblast cell line from the sister (P7-1) revealed significantly reduced rates of replication fork progression in the presence of camptothecin. Unusual features in the sibs included the lack of short stature and the presence of neutropenia.

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

Last Updated: May 16, 2025