rs763118922
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000359520.12(TECPR2):c.2876G>A(p.Arg959Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,608,784 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. R959W) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TECPR2 | NM_014844.5 | c.2876G>A | p.Arg959Gln | missense_variant | 12/20 | ENST00000359520.12 | NP_055659.2 | |
TECPR2 | NM_001172631.3 | c.2876G>A | p.Arg959Gln | missense_variant | 12/17 | NP_001166102.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TECPR2 | ENST00000359520.12 | c.2876G>A | p.Arg959Gln | missense_variant | 12/20 | 1 | NM_014844.5 | ENSP00000352510 | P1 | |
TECPR2 | ENST00000558678.1 | c.2876G>A | p.Arg959Gln | missense_variant | 12/17 | 1 | ENSP00000453671 | |||
TECPR2 | ENST00000557786.1 | n.485G>A | non_coding_transcript_exon_variant | 3/4 | 4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152102Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249564Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134996
GnomAD4 exome AF: 0.00000549 AC: 8AN: 1456682Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3AN XY: 724656
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74292
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 49 Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 27, 2021 | This sequence change replaces arginine with glutamine at codon 959 of the TECPR2 protein (p.Arg959Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs763118922, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with TECPR2-related conditions. 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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