NM_003239.5(TGFB3):c.559G>A (p.Gly187Ser) AND Rienhoff syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 26, 2023
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:: RCV002515260.10

Allele description [Variation Report for NM_003239.5(TGFB3):c.559G>A (p.Gly187Ser)]

NM_003239.5(TGFB3):c.559G>A (p.Gly187Ser)

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.559G>A (p.Gly187Ser)

HGVS:

NC_000014.9:g.75971213C>T
NG_011715.1:g.15537G>A
NM_001329938.2:c.559G>A
NM_001329939.2:c.559G>A
NM_003239.5:c.559G>AMANE SELECT
NP_001316867.1:p.Gly187Ser
NP_001316868.1:p.Gly187Ser
NP_003230.1:p.Gly187Ser
NP_003230.1:p.Gly187Ser
LRG_399t1:c.559G>A
LRG_399:g.15537G>A
NC_000014.8:g.76437556C>T
NM_003239.2:c.559G>A
NM_003239.3:c.559G>A
NM_003239.4:c.559G>A
p.Gly187Ser

Protein change:

G187S

Links:

dbSNP: rs201063101

NCBI 1000 Genomes Browser:

rs201063101

Molecular consequence:

NM_001329938.2:c.559G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001329939.2:c.559G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003239.5:c.559G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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HLA-DMA major histocompatibility complex, class II, DM alpha [Homo sapiens]
Gene ID:3108

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000776802	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 26, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29907982, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000776802

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 26, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Results of next-generation sequencing gene panel diagnostics including copy-number variation analysis in 810 patients suspected of heritable thoracic aortic disorders.

Overwater E, Marsili L, Baars MJH, Baas AF, van de Beek I, Dulfer E, van Hagen JM, Hilhorst-Hofstee Y, Kempers M, Krapels IP, Menke LA, Verhagen JMA, Yeung KK, Zwijnenburg PJG, Groenink M, van Rijn P, Weiss MM, Voorhoeve E, van Tintelen JP, Houweling AC, Maugeri A.

Hum Mutat. 2018 Sep;39(9):1173-1192. doi: 10.1002/humu.23565. Epub 2018 Jul 12.

PubMed [citation]

PMID:: 29907982
PMCID:: PMC6175145

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000776802.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TGFB3 protein function. ClinVar contains an entry for this variant (Variation ID: 191778). This missense change has been observed in individual(s) with clinical features of TGFB3-related conditions (PMID: 29907982). This variant is present in population databases (rs201063101, gnomAD 0.007%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 187 of the TGFB3 protein (p.Gly187Ser).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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