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NM_003239.5(TGFB3):c.517-1G>C AND Rienhoff syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 20, 2018
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:
RCV002544847.10

Allele description [Variation Report for NM_003239.5(TGFB3):c.517-1G>C]

NM_003239.5(TGFB3):c.517-1G>C

Gene:
TGFB3:transforming growth factor beta 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q24.3
Genomic location:
Preferred name:
NM_003239.5(TGFB3):c.517-1G>C
HGVS:
  • NC_000014.9:g.75971256C>G
  • NG_011715.1:g.15494G>C
  • NM_001329938.2:c.517-1G>C
  • NM_001329939.2:c.517-1G>C
  • NM_003239.5:c.517-1G>CMANE SELECT
  • LRG_399:g.15494G>C
  • NC_000014.8:g.76437599C>G
  • NM_003239.3:c.517-1G>C
Links:
dbSNP: rs1566682530
NCBI 1000 Genomes Browser:
rs1566682530
Molecular consequence:
  • NM_001329938.2:c.517-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001329939.2:c.517-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_003239.5:c.517-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Rienhoff syndrome
Synonyms:
Loeys-Dietz syndrome 5
Identifiers:
MONDO: MONDO:0014262; MedGen: C3810012; OMIM: 615582

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000817209Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jun 20, 2018) 		germlineclinical testing

PubMed (3)
[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

Mutations in a TGF-β ligand, TGFB3, cause syndromic aortic aneurysms and dissections.

Bertoli-Avella AM, Gillis E, Morisaki H, Verhagen JMA, de Graaf BM, van de Beek G, Gallo E, Kruithof BPT, Venselaar H, Myers LA, Laga S, Doyle AJ, Oswald G, van Cappellen GWA, Yamanaka I, van der Helm RM, Beverloo B, de Klein A, Pardo L, Lammens M, Evers C, Devriendt K, et al.

J Am Coll Cardiol. 2015 Apr 7;65(13):1324-1336. doi: 10.1016/j.jacc.2015.01.040.

PubMed [citation]
PMID:
25835445
PMCID:
PMC4380321
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000817209.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change affects an acceptor splice site in intron 2 of the TGFB3 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TGFB3-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TGFB3 are known to be pathogenic (PMID: 25835445). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 3, 2024