rs1555795056
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_001387283.1(SMARCA4):c.4592A>C(p.Glu1531Ala) variant causes a missense change involving the alteration of a 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1531D) has been classified as Likely benign.
Frequency
Consequence
NM_001387283.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCA4 | NM_001387283.1 | c.4592A>C | p.Glu1531Ala | missense_variant | 32/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.4496A>C | p.Glu1499Ala | missense_variant | 31/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.4592A>C | p.Glu1531Ala | missense_variant | 32/36 | NM_001387283.1 | |||
SMARCA4 | ENST00000344626.10 | c.4496A>C | p.Glu1499Ala | missense_variant | 31/35 | 1 | NM_003072.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
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 13, 2017 | In summary, this variant has uncertain impact on SMARCA4 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with a SMARCA4-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with alanine at codon 1531 of the SMARCA4 protein (p.Glu1531Ala). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and alanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at