rs200124801
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000266732.8(TMPO):āc.1048C>Gā(p.Gln350Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,614,076 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 ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q350R) has been classified as Likely benign.
Frequency
Consequence
ENST00000266732.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPO | NM_001032283.3 | c.565+1467C>G | intron_variant | ENST00000556029.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPO | ENST00000556029.6 | c.565+1467C>G | intron_variant | 1 | NM_001032283.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251068Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135730
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461776Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727196
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152300Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74478
ClinVar
Submissions by phenotype
Loeys-Dietz syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 350 of the TMPO protein (p.Gln350Glu). This variant is present in population databases (rs200124801, gnomAD 0.006%). 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: 1014533). 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 with a negative predictive value of 80%. 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