rs767216575
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The ENST00000266732.8(TMPO):c.2048T>A(p.Val683Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,612,928 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V683V) has been classified as Likely benign.
Frequency
Consequence
ENST00000266732.8 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMPO | NM_001032283.3 | c.565+2467T>A | intron_variant | ENST00000556029.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMPO | ENST00000556029.6 | c.565+2467T>A | intron_variant | 1 | NM_001032283.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152144Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249378Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135146
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1460784Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24AN XY: 726742
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152144Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74334
ClinVar
Submissions by phenotype
Loeys-Dietz syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2022 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 239534). This variant has not been reported in the literature in individuals affected with TMPO-related conditions. This variant is present in population databases (rs767216575, gnomAD 0.004%). This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 683 of the TMPO protein (p.Val683Glu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at