rs201704673
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The ENST00000359520.12(TECPR2):c.3797G>T(p.Gly1266Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,613,720 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. G1266R) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000359520.12 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TECPR2 | NM_014844.5 | c.3797G>T | p.Gly1266Val | missense_variant | 18/20 | ENST00000359520.12 | NP_055659.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TECPR2 | ENST00000359520.12 | c.3797G>T | p.Gly1266Val | missense_variant | 18/20 | 1 | NM_014844.5 | ENSP00000352510 | P1 | |
TECPR2 | ENST00000561099.1 | n.106G>T | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000838 AC: 21AN: 250672Hom.: 0 AF XY: 0.0000738 AC XY: 10AN XY: 135478
GnomAD4 exome AF: 0.000127 AC: 185AN: 1461486Hom.: 0 Cov.: 31 AF XY: 0.000106 AC XY: 77AN XY: 727068
GnomAD4 genome AF: 0.000105 AC: 16AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74378
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 28, 2024 | - - |
Hereditary spastic paraplegia 49 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 20, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1266 of the TECPR2 protein (p.Gly1266Val). This variant is present in population databases (rs201704673, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TECPR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 572101). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Feb 01, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at