rs1555753732
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_003072.5(SMARCA4):c.714_719delCGGCCC(p.Gly239_Pro240del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P238P) has been classified as Likely benign.
Frequency
Consequence
NM_003072.5 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.714_719delCGGCCC | p.Gly239_Pro240del | disruptive_inframe_deletion | Exon 4 of 36 | ENST00000646693.2 | NP_001374212.1 | |
SMARCA4 | NM_003072.5 | c.714_719delCGGCCC | p.Gly239_Pro240del | disruptive_inframe_deletion | Exon 4 of 35 | ENST00000344626.10 | NP_003063.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.714_719delCGGCCC | p.Gly239_Pro240del | disruptive_inframe_deletion | Exon 4 of 36 | NM_001387283.1 | ENSP00000495368.1 | |||
SMARCA4 | ENST00000344626.10 | c.714_719delCGGCCC | p.Gly239_Pro240del | disruptive_inframe_deletion | Exon 4 of 35 | 1 | NM_003072.5 | ENSP00000343896.4 | ||
SMARCA4 | ENST00000643549.1 | c.714_719delCGGCCC | p.Gly239_Pro240del | disruptive_inframe_deletion | Exon 4 of 35 | ENSP00000493975.1 | ||||
SMARCA4 | ENST00000541122.6 | c.714_719delCGGCCC | p.Gly239_Pro240del | disruptive_inframe_deletion | Exon 5 of 35 | 5 | ENSP00000445036.2 | |||
SMARCA4 | ENST00000643296.1 | c.714_719delCGGCCC | p.Gly239_Pro240del | disruptive_inframe_deletion | Exon 4 of 34 | ENSP00000496635.1 | ||||
SMARCA4 | ENST00000644737.1 | c.714_719delCGGCCC | p.Gly239_Pro240del | disruptive_inframe_deletion | Exon 4 of 34 | ENSP00000495548.1 | ||||
SMARCA4 | ENST00000589677.5 | c.714_719delCGGCCC | p.Gly239_Pro240del | disruptive_inframe_deletion | Exon 5 of 35 | 5 | ENSP00000464778.1 | |||
SMARCA4 | ENST00000643995.1 | c.126_131delCGGCCC | p.Gly43_Pro44del | disruptive_inframe_deletion | Exon 1 of 32 | ENSP00000496004.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Uncertain:1
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. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. This variant has not been reported in the literature in individuals with SMARCA4-related disease. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant, c.714_719delCGGCCC, results in the deletion of 2 amino acids of the SMARCA4 protein (p.Gly243_Pro244del), but otherwise preserves the integrity of the reading frame. -
Hereditary cancer-predisposing syndrome Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at