rs199573401
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001387283.1(SMARCA4):āc.862C>Gā(p.Pro288Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,460,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P288S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001387283.1 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.862C>G | p.Pro288Ala | missense_variant, splice_region_variant | 6/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.862C>G | p.Pro288Ala | missense_variant, splice_region_variant | 6/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.862C>G | p.Pro288Ala | missense_variant, splice_region_variant | 6/36 | NM_001387283.1 | |||
SMARCA4 | ENST00000344626.10 | c.862C>G | p.Pro288Ala | missense_variant, splice_region_variant | 6/35 | 1 | NM_003072.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000414 AC: 1AN: 241654Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 131796
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460796Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726712
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 05, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. This variant is present in population databases (rs199573401, gnomAD 0.001%). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 288 of the SMARCA4 protein (p.Pro288Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at