rs281865484
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000660.7(TGFB1):c.505G>C(p.Glu169Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000660.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TGFB1 | NM_000660.7 | c.505G>C | p.Glu169Gln | missense_variant | Exon 2 of 7 | ENST00000221930.6 | NP_000651.3 | |
TGFB1 | XM_011527242.3 | c.505G>C | p.Glu169Gln | missense_variant | Exon 2 of 7 | XP_011525544.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TGFB1 | ENST00000221930.6 | c.505G>C | p.Glu169Gln | missense_variant | Exon 2 of 7 | 1 | NM_000660.7 | ENSP00000221930.4 | ||
TGFB1 | ENST00000597453.1 | n.36G>C | non_coding_transcript_exon_variant | Exon 1 of 3 | 1 | |||||
TGFB1 | ENST00000600196.2 | c.505G>C | p.Glu169Gln | missense_variant | Exon 2 of 6 | 5 | ENSP00000504008.1 | |||
TGFB1 | ENST00000677934.1 | c.505G>C | p.Glu169Gln | missense_variant | Exon 2 of 5 | ENSP00000504769.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251336Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135848
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460814Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726726
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 169 of the TGFB1 protein (p.Glu169Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TGFB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1920186). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TGFB1 protein function with a negative predictive value of 80%. This variant disrupts the p.Glu169 amino acid residue in TGFB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17433803, 29230158, 29620655). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at