rs368004396
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_003239.5(TGFB3):c.580C>T(p.Arg194Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R194P) has been classified as Uncertain significance.
Frequency
Consequence
NM_003239.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFB3 | NM_003239.5 | c.580C>T | p.Arg194Trp | missense_variant | 3/7 | ENST00000238682.8 | |
TGFB3 | NM_001329939.2 | c.580C>T | p.Arg194Trp | missense_variant | 4/8 | ||
TGFB3 | NM_001329938.2 | c.580C>T | p.Arg194Trp | missense_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFB3 | ENST00000238682.8 | c.580C>T | p.Arg194Trp | missense_variant | 3/7 | 1 | NM_003239.5 | P1 | |
TGFB3-AS1 | ENST00000553732.1 | n.269G>A | non_coding_transcript_exon_variant | 1/2 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251288Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135806
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727228
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 07, 2021 | The p.R194W variant (also known as c.580C>T), located in coding exon 3 of the TGFB3 gene, results from a C to T substitution at nucleotide position 580. The arginine at codon 194 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is not 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 | Nov 05, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 24, 2023 | Has been reported as a variant of uncertain significance in an individual with dilated cardiomyopathy (Burstein et al., 2021); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32746448) - |
Rienhoff syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2022 | ClinVar contains an entry for this variant (Variation ID: 410271). 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32746448). This variant is present in population databases (rs368004396, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 194 of the TGFB3 protein (p.Arg194Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at