rs1555877290
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP3
The NM_003073.5(SMARCB1):c.613A>T(p.Thr205Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. T205I) has been classified as Uncertain significance.
Frequency
Consequence
NM_003073.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCB1 | NM_003073.5 | c.613A>T | p.Thr205Ser | missense_variant | 5/9 | ENST00000644036.2 | |
SMARCB1 | NM_001362877.2 | c.667A>T | p.Thr223Ser | missense_variant | 5/9 | ||
SMARCB1 | NM_001317946.2 | c.640A>T | p.Thr214Ser | missense_variant | 5/9 | ||
SMARCB1 | NM_001007468.3 | c.586A>T | p.Thr196Ser | missense_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCB1 | ENST00000644036.2 | c.613A>T | p.Thr205Ser | missense_variant | 5/9 | NM_003073.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD4 exome Cov.: 34
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 30, 2017 | 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SMARCB1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with serine at codon 205 of the SMARCB1 protein (p.Thr205Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at