rs754951098
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The ENST00000266732.8(TMPO):āc.1030A>Gā(p.Arg344Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
ENST00000266732.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMPO | NM_001032283.3 | c.565+1449A>G | intron_variant | ENST00000556029.6 | NP_001027454.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMPO | ENST00000556029.6 | c.565+1449A>G | intron_variant | 1 | NM_001032283.3 | ENSP00000450627 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250884Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135676
GnomAD4 exome AF: 0.0000650 AC: 95AN: 1461740Hom.: 0 Cov.: 32 AF XY: 0.0000523 AC XY: 38AN XY: 727176
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 10, 2023 | The p.R344G variant (also known as c.1030A>G), located in coding exon 4 of the TMPO gene, results from an A to G substitution at nucleotide position 1030. The arginine at codon 344 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. - |
Loeys-Dietz syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 13, 2023 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 344 of the TMPO protein (p.Arg344Gly). This variant is present in population databases (rs754951098, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with TMPO-related conditions. ClinVar contains an entry for this variant (Variation ID: 574819). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TMPO protein function. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 17, 2019 | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at