rs371230847
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_003239.5(TGFB3):c.235C>G(p.Leu79Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,614,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. L79L) has been classified as Likely benign.
Frequency
Consequence
NM_003239.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFB3 | NM_003239.5 | c.235C>G | p.Leu79Val | missense_variant | 1/7 | ENST00000238682.8 | |
TGFB3 | NM_001329939.2 | c.235C>G | p.Leu79Val | missense_variant | 2/8 | ||
TGFB3 | NM_001329938.2 | c.235C>G | p.Leu79Val | missense_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFB3 | ENST00000238682.8 | c.235C>G | p.Leu79Val | missense_variant | 1/7 | 1 | NM_003239.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000525 AC: 8AN: 152240Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251474Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135908
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74384
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 20, 2024 | The p.L79V variant (also known as c.235C>G), located in coding exon 1 of the TGFB3 gene, results from a C to G substitution at nucleotide position 235. The leucine at codon 79 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Arrhythmogenic right ventricular dysplasia 1;C3810012:Rienhoff syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 30, 2021 | - - |
Rienhoff syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 06, 2022 | This variant has not been reported in the literature in individuals affected with TGFB3-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 579759). This variant is present in population databases (rs371230847, gnomAD 0.03%). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 79 of the TGFB3 protein (p.Leu79Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at