17-75522138-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_207346.3(TSEN54):c.1057C>T(p.Arg353Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000856 in 1,564,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. R353L) has been classified as Uncertain significance.
Frequency
Consequence
NM_207346.3 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 |
---|---|---|---|---|---|---|---|
TSEN54 | NM_207346.3 | c.1057C>T | p.Arg353Trp | missense_variant | 8/11 | ENST00000333213.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSEN54 | ENST00000333213.11 | c.1057C>T | p.Arg353Trp | missense_variant | 8/11 | 1 | NM_207346.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000135 AC: 24AN: 178398Hom.: 0 AF XY: 0.000178 AC XY: 17AN XY: 95766
GnomAD4 exome AF: 0.0000708 AC: 100AN: 1412424Hom.: 0 Cov.: 72 AF XY: 0.0000760 AC XY: 53AN XY: 697478
GnomAD4 genome AF: 0.000223 AC: 34AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74484
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 07, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 353 of the TSEN54 protein (p.Arg353Trp). This variant is present in population databases (rs200540627, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with TSEN54-related conditions. ClinVar contains an entry for this variant (Variation ID: 212449). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSEN54 protein function. 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 20, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.1057C>T (p.R353W) alteration is located in exon 8 (coding exon 8) of the TSEN54 gene. This alteration results from a C to T substitution at nucleotide position 1057, causing the arginine (R) at amino acid position 353 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Pontocerebellar hypoplasia type 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 31, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at