rs150445385
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The ENST00000266732.8(TMPO):c.1829G>A(p.Arg610His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,611,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. R610C) has been classified as Likely benign.
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 | UniProt |
---|---|---|---|---|---|---|---|
TMPO | NM_001032283.3 | c.565+2248G>A | intron_variant | ENST00000556029.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPO | ENST00000556029.6 | c.565+2248G>A | intron_variant | 1 | NM_001032283.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250096Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135196
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459660Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4AN XY: 725660
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74480
ClinVar
Submissions by phenotype
Loeys-Dietz syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2018 | In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant is present in population databases (rs150445385, ExAC 0.03%) but has not been reported in the literature in individuals with a TMPO-related disease. This sequence change replaces arginine with histidine at codon 610 of the TMPO protein (p.Arg610His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at