rs370462085
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_014844.5(TECPR2):c.1415C>T(p.Thr472Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000433 in 1,407,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_014844.5 missense, splice_region
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 | UniProt |
---|---|---|---|---|---|---|---|
TECPR2 | NM_014844.5 | c.1415C>T | p.Thr472Ile | missense_variant, splice_region_variant | 8/20 | ENST00000359520.12 | |
TECPR2 | NM_001172631.3 | c.1415C>T | p.Thr472Ile | missense_variant, splice_region_variant | 8/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECPR2 | ENST00000359520.12 | c.1415C>T | p.Thr472Ile | missense_variant, splice_region_variant | 8/20 | 1 | NM_014844.5 | P1 | |
TECPR2 | ENST00000558678.1 | c.1415C>T | p.Thr472Ile | missense_variant, splice_region_variant | 8/17 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.0000433 AC: 61AN: 1407924Hom.: 0 Cov.: 31 AF XY: 0.0000461 AC XY: 32AN XY: 694346
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 49 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2022 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 472 of the TECPR2 protein (p.Thr472Ile). This variant is not present in population databases (gnomAD no frequency). 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: 408915). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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