rs1555752859
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001387283.1(SMARCA4):c.365C>A(p.Ser122Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. S122S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001387283.1 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.365C>A | p.Ser122Ter | stop_gained | 4/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.365C>A | p.Ser122Ter | stop_gained | 4/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.365C>A | p.Ser122Ter | stop_gained | 4/36 | NM_001387283.1 | |||
SMARCA4 | ENST00000344626.10 | c.365C>A | p.Ser122Ter | stop_gained | 4/35 | 1 | NM_003072.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461462Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727070
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2019 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SMARCA4 are known to be pathogenic (PMID: 24658001, 24658002). This variant has not been reported in the literature in individuals with SMARCA4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser122*) in the SMARCA4 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at