chr19-10986523-C-CGGCCCG
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP3BP6
The NM_001387283.1(SMARCA4):c.695_696insGGGCCC(p.Gly243_Pro244dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.000000719 in 1,391,208 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P230P) has been classified as Likely benign.
Frequency
Consequence
NM_001387283.1 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.695_696insGGGCCC | p.Gly243_Pro244dup | inframe_insertion | 4/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.695_696insGGGCCC | p.Gly243_Pro244dup | inframe_insertion | 4/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000344626.10 | c.695_696insGGGCCC | p.Gly243_Pro244dup | inframe_insertion | 4/35 | 1 | NM_003072.5 | P4 | |
SMARCA4 | ENST00000646693.2 | c.695_696insGGGCCC | p.Gly243_Pro244dup | inframe_insertion | 4/36 | NM_001387283.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 7.19e-7 AC: 1AN: 1391208Hom.: 0 Cov.: 34 AF XY: 0.00000146 AC XY: 1AN XY: 686496
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 11, 2023 | This variant, c.695_696insGGGCCC, results in the insertion of 2 amino acid(s) of the SMARCA4 protein (p.Gly243_Pro244dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 470450). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 25, 2021 | 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