rs768423844
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PP3BS2
The NM_003239.5(TGFB3):c.908A>C(p.Asp303Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003239.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TGFB3 | NM_003239.5 | c.908A>C | p.Asp303Ala | missense_variant | Exon 5 of 7 | ENST00000238682.8 | NP_003230.1 | |
TGFB3 | NM_001329939.2 | c.908A>C | p.Asp303Ala | missense_variant | Exon 6 of 8 | NP_001316868.1 | ||
TGFB3 | NM_001329938.2 | c.908A>C | p.Asp303Ala | missense_variant | Exon 5 of 5 | NP_001316867.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251378Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135858
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461822Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727192
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 1;C3810012:Rienhoff syndrome Uncertain:1
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Rienhoff syndrome Uncertain:1
This variant has not been reported in the literature in individuals with TGFB3-related disease. 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 is present in population databases (rs768423844, ExAC 0.004%). This sequence change replaces aspartic acid with alanine at codon 303 of the TGFB3 protein (p.Asp303Ala). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and alanine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at