rs200943582
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_001032283.3(TMPO):c.382G>A(p.Gly128Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,748 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G128E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001032283.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPO | NM_001032283.3 | c.382G>A | p.Gly128Arg | missense_variant | 2/9 | ENST00000556029.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPO | ENST00000556029.6 | c.382G>A | p.Gly128Arg | missense_variant | 2/9 | 1 | NM_001032283.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251408Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135872
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461620Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727118
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74322
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Loeys-Dietz syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2022 | This variant is present in population databases (rs200943582, 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 191788). This variant has not been reported in the literature in individuals affected with TMPO-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 128 of the TMPO protein (p.Gly128Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at