chr14-102450629-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014844.5(TECPR2):c.3386C>A(p.Ser1129Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000304 in 1,614,186 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. S1129S) 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.3386C>A | p.Ser1129Tyr | missense_variant | 15/20 | ENST00000359520.12 | |
TECPR2 | NM_001172631.3 | c.3386C>A | p.Ser1129Tyr | missense_variant | 15/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECPR2 | ENST00000359520.12 | c.3386C>A | p.Ser1129Tyr | missense_variant | 15/20 | 1 | NM_014844.5 | P1 | |
TECPR2 | ENST00000558678.1 | c.3386C>A | p.Ser1129Tyr | missense_variant | 15/17 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000328 AC: 50AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000274 AC: 69AN: 251444Hom.: 0 AF XY: 0.000302 AC XY: 41AN XY: 135904
GnomAD4 exome AF: 0.000301 AC: 440AN: 1461860Hom.: 0 Cov.: 31 AF XY: 0.000278 AC XY: 202AN XY: 727234
GnomAD4 genome AF: 0.000328 AC: 50AN: 152326Hom.: 0 Cov.: 33 AF XY: 0.000349 AC XY: 26AN XY: 74496
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 49 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 25, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 22, 2022 | This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1129 of the TECPR2 protein (p.Ser1129Tyr). This variant is present in population databases (rs139247564, gnomAD 0.06%). 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: 540301). 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: "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 | Jan 26, 2022 | The c.3386C>A (p.S1129Y) alteration is located in exon 15 (coding exon 14) of the TECPR2 gene. This alteration results from a C to A substitution at nucleotide position 3386, causing the serine (S) at amino acid position 1129 to be replaced by a tyrosine (Y). 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 | - - |
Inherited spastic paresis Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at