19-11010421-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001387283.1(SMARCA4):c.2164C>T(p.Gln722Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Q722Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001387283.1 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.2164C>T | p.Gln722Ter | stop_gained | 15/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.2164C>T | p.Gln722Ter | stop_gained | 15/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.2164C>T | p.Gln722Ter | stop_gained | 15/36 | NM_001387283.1 | |||
SMARCA4 | ENST00000344626.10 | c.2164C>T | p.Gln722Ter | stop_gained | 15/35 | 1 | NM_003072.5 | P4 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2017 | This variant is not present in population databases (ExAC no frequency). 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 disease. This sequence change creates a premature translational stop signal (p.Gln722*) 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