rs777295398
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_003072.5(SMARCA4):c.1420-3C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003072.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.1420-3C>G | splice_region_variant, intron_variant | Intron 8 of 35 | ENST00000646693.2 | NP_001374212.1 | ||
SMARCA4 | NM_003072.5 | c.1420-3C>G | splice_region_variant, intron_variant | Intron 8 of 34 | ENST00000344626.10 | NP_003063.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.1420-3C>G | splice_region_variant, intron_variant | Intron 8 of 35 | NM_001387283.1 | ENSP00000495368.1 | ||||
SMARCA4 | ENST00000344626.10 | c.1420-3C>G | splice_region_variant, intron_variant | Intron 8 of 34 | 1 | NM_003072.5 | ENSP00000343896.4 | |||
SMARCA4 | ENST00000643549.1 | c.1420-3C>G | splice_region_variant, intron_variant | Intron 8 of 34 | ENSP00000493975.1 | |||||
SMARCA4 | ENST00000541122.6 | c.1420-3C>G | splice_region_variant, intron_variant | Intron 9 of 34 | 5 | ENSP00000445036.2 | ||||
SMARCA4 | ENST00000643296.1 | c.1420-3C>G | splice_region_variant, intron_variant | Intron 8 of 33 | ENSP00000496635.1 | |||||
SMARCA4 | ENST00000644737.1 | c.1420-3C>G | splice_region_variant, intron_variant | Intron 8 of 33 | ENSP00000495548.1 | |||||
SMARCA4 | ENST00000589677.5 | c.1420-3C>G | splice_region_variant, intron_variant | Intron 9 of 34 | 5 | ENSP00000464778.1 | ||||
SMARCA4 | ENST00000643995.1 | c.832-3C>G | splice_region_variant, intron_variant | Intron 5 of 31 | ENSP00000496004.1 | |||||
SMARCA4 | ENST00000644963.1 | c.64-3C>G | splice_region_variant, intron_variant | Intron 1 of 27 | ENSP00000495599.1 | |||||
SMARCA4 | ENST00000644065.1 | c.148-3C>G | splice_region_variant, intron_variant | Intron 1 of 26 | ENSP00000493615.1 | |||||
SMARCA4 | ENST00000642350.1 | c.-96C>G | upstream_gene_variant | ENSP00000495355.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Uncertain:1
This variant has not been reported in the literature in individuals with SMARCA4-related conditions. 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 8 of the SMARCA4 gene. It does not directly change the encoded amino acid sequence of the SMARCA4 protein, but it affects a nucleotide within the consensus splice site of the intron. -
Hereditary cancer-predisposing syndrome Uncertain:1
The c.1420-3C>G intronic variant results from a C to G substitution 3 nucleotides upstream from coding exon 8 in the SMARCA4 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice acceptor site. 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