rs779769475
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1
The NM_003073.5(SMARCB1):c.158G>A(p.Arg53Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,602 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003073.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCB1 | NM_003073.5 | c.158G>A | p.Arg53Gln | missense_variant | Exon 2 of 9 | ENST00000644036.2 | NP_003064.2 | |
SMARCB1 | NM_001362877.2 | c.158G>A | p.Arg53Gln | missense_variant | Exon 2 of 9 | NP_001349806.1 | ||
SMARCB1 | NM_001317946.2 | c.158G>A | p.Arg53Gln | missense_variant | Exon 2 of 9 | NP_001304875.1 | ||
SMARCB1 | NM_001007468.3 | c.158G>A | p.Arg53Gln | missense_variant | Exon 2 of 9 | NP_001007469.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251486Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135918
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461410Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727028
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:2
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; This variant is associated with the following publications: (PMID: 28692054, 26073604) -
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 53 of the SMARCB1 protein (p.Arg53Gln). This variant is present in population databases (rs779769475, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with SMARCB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2184420). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -
Hereditary cancer-predisposing syndrome Uncertain:1
The p.R53Q variant (also known as c.158G>A), located in coding exon 2 of the SMARCB1 gene, results from a G to A substitution at nucleotide position 158. The arginine at codon 53 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at