rs147165460
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_207346.3(TSEN54):c.622C>T(p.Arg208Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,613,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_207346.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSEN54 | NM_207346.3 | c.622C>T | p.Arg208Trp | missense_variant, splice_region_variant | 7/11 | ENST00000333213.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSEN54 | ENST00000333213.11 | c.622C>T | p.Arg208Trp | missense_variant, splice_region_variant | 7/11 | 1 | NM_207346.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000757 AC: 19AN: 251144Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135808
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461580Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25AN XY: 727100
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74466
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 08, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 24, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 208 of the TSEN54 protein (p.Arg208Trp). This variant is present in population databases (rs147165460, gnomAD 0.03%). 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: 198637). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tryptophan amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 11, 2023 | - - |
Pontocerebellar hypoplasia type 2A;C1856974:Pontocerebellar hypoplasia type 4;C1857762:Pontocerebellar hypoplasia type 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at