22-23787167-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003073.5(SMARCB1):c.-3G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,450,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
SMARCB1
NM_003073.5 5_prime_UTR
NM_003073.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.28
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SMARCB1 | NM_003073.5 | c.-3G>A | 5_prime_UTR_variant | 1/9 | ENST00000644036.2 | NP_003064.2 | ||
| SMARCB1 | NM_001007468.3 | c.-3G>A | 5_prime_UTR_variant | 1/9 | NP_001007469.1 | |||
| SMARCB1 | NM_001317946.2 | c.-3G>A | 5_prime_UTR_variant | 1/9 | NP_001304875.1 | |||
| SMARCB1 | NM_001362877.2 | c.-3G>A | 5_prime_UTR_variant | 1/9 | NP_001349806.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SMARCB1 | ENST00000644036.2 | c.-3G>A | 5_prime_UTR_variant | 1/9 | NM_003073.5 | ENSP00000494049 | A1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000276 AC: 4AN: 1450380Hom.: 0 Cov.: 29 AF XY: 0.00000277 AC XY: 2AN XY: 722084
GnomAD4 exome
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4
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1450380
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29
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2
AN XY:
722084
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GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 17, 2024 | The c.-3G>A variant is located in the 5' untranslated region (5’ UTR) of the SMARCB1 gene. This variant results from a G to A substitution 3 bases upstream from the first translated codon. This nucleotide position is well conserved in available vertebrate species. Based on the available evidence, the clinical significance of this variant remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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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
Publications
No publications associated with this variant yet.