14-75980730-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003239.5(TGFB3):āc.164G>Cā(p.Ser55Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S55N) has been classified as Likely benign.
Frequency
Consequence
NM_003239.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFB3 | NM_003239.5 | c.164G>C | p.Ser55Thr | missense_variant | 1/7 | ENST00000238682.8 | |
TGFB3 | NM_001329939.2 | c.164G>C | p.Ser55Thr | missense_variant | 2/8 | ||
TGFB3 | NM_001329938.2 | c.164G>C | p.Ser55Thr | missense_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFB3 | ENST00000238682.8 | c.164G>C | p.Ser55Thr | missense_variant | 1/7 | 1 | NM_003239.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251492Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135922
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727248
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74468
ClinVar
Submissions by phenotype
Rienhoff syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2022 | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 55 of the TGFB3 protein (p.Ser55Thr). This variant is present in population databases (rs143229915, gnomAD 0.003%). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with TGFB3-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at