rs751957510
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014844.5(TECPR2):c.1471G>A(p.Glu491Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000973 in 1,388,140 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E491E) has been classified as Likely benign.
Frequency
Consequence
NM_014844.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECPR2 | NM_014844.5 | c.1471G>A | p.Glu491Lys | missense_variant | 9/20 | ENST00000359520.12 | |
TECPR2 | NM_001172631.3 | c.1471G>A | p.Glu491Lys | missense_variant | 9/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECPR2 | ENST00000359520.12 | c.1471G>A | p.Glu491Lys | missense_variant | 9/20 | 1 | NM_014844.5 | P1 | |
TECPR2 | ENST00000558678.1 | c.1471G>A | p.Glu491Lys | missense_variant | 9/17 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000144 AC: 22AN: 152736Hom.: 0 AF XY: 0.000210 AC XY: 17AN XY: 81128
GnomAD4 exome AF: 0.000104 AC: 129AN: 1236006Hom.: 0 Cov.: 29 AF XY: 0.000109 AC XY: 65AN XY: 594928
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 49 Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 30, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 28, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 491 of the TECPR2 protein (p.Glu491Lys). This variant is present in population databases (rs751957510, 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: 240923). 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: "Possibly 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 | Dec 19, 2022 | The c.1471G>A (p.E491K) alteration is located in exon 9 (coding exon 8) of the TECPR2 gene. This alteration results from a G to A substitution at nucleotide position 1471, causing the glutamic acid (E) at amino acid position 491 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 12, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | TECPR2: BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at