rs1555875915
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_003073.5(SMARCB1):c.178_179del(p.Arg60GlufsTer10) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. E58E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
SMARCB1
NM_003073.5 frameshift
NM_003073.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.70
Genes affected
SMARCB1 (HGNC:11103): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 22-23791835-AAG-A is Pathogenic according to our data. Variant chr22-23791835-AAG-A is described in ClinVar as [Pathogenic]. Clinvar id is 486500.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCB1 | NM_003073.5 | c.178_179del | p.Arg60GlufsTer10 | frameshift_variant | 2/9 | ENST00000644036.2 | |
SMARCB1 | NM_001007468.3 | c.178_179del | p.Arg60GlufsTer9 | frameshift_variant | 2/9 | ||
SMARCB1 | NM_001317946.2 | c.178_179del | p.Arg60GlufsTer9 | frameshift_variant | 2/9 | ||
SMARCB1 | NM_001362877.2 | c.178_179del | p.Arg60GlufsTer10 | frameshift_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCB1 | ENST00000644036.2 | c.178_179del | p.Arg60GlufsTer10 | frameshift_variant | 2/9 | NM_003073.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 06, 2017 | The c.178_179delAG pathogenic mutation, located in coding exon 2 of the SMARCB1 gene, results from a deletion of two nucleotides at nucleotide positions 178 to 179, causing a translational frameshift with a predicted alternate stop codon (p.R60Efs*10). A different deletion resulting in a stop codon at the same position (c.170_171delTG p.V57Gfs*13) has been identified in a patient with a central nervous system atypical teratoid rhabdoid tumor (AR/RT) at age 5 months (Kordes U et al. Genes Chromosomes Cancer, 2010 Feb;49:176-81). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at