rs140434256
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014844.5(TECPR2):c.2900C>T(p.Pro967Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000525 in 1,598,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P967P) has been classified as Likely benign.
Frequency
Consequence
NM_014844.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECPR2 | NM_014844.5 | c.2900C>T | p.Pro967Leu | missense_variant | 12/20 | ENST00000359520.12 | |
TECPR2 | NM_001172631.3 | c.2900C>T | p.Pro967Leu | missense_variant | 12/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECPR2 | ENST00000359520.12 | c.2900C>T | p.Pro967Leu | missense_variant | 12/20 | 1 | NM_014844.5 | P1 | |
TECPR2 | ENST00000558678.1 | c.2900C>T | p.Pro967Leu | missense_variant | 12/17 | 1 | |||
TECPR2 | ENST00000557786.1 | n.509C>T | non_coding_transcript_exon_variant | 3/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000921 AC: 14AN: 152056Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000650 AC: 16AN: 246244Hom.: 0 AF XY: 0.0000825 AC XY: 11AN XY: 133408
GnomAD4 exome AF: 0.0000484 AC: 70AN: 1446566Hom.: 0 Cov.: 30 AF XY: 0.0000557 AC XY: 40AN XY: 718760
GnomAD4 genome ? AF: 0.0000921 AC: 14AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74254
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 49 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 18, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces proline with leucine at codon 967 of the TECPR2 protein (p.Pro967Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs140434256, ExAC 0.01%). 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: "Tolerated"; 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 15, 2021 | The c.2900C>T (p.P967L) alteration is located in exon 12 (coding exon 11) of the TECPR2 gene. This alteration results from a C to T substitution at nucleotide position 2900, causing the proline (P) at amino acid position 967 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at