rs878854210
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001387283.1(SMARCA4):c.2533G>A(p.Val845Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,612,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. V845F) has been classified as Uncertain significance.
Frequency
Consequence
NM_001387283.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.2533G>A | p.Val845Ile | missense_variant | 18/36 | ENST00000646693.2 | |
SMARCA4 | NM_003072.5 | c.2533G>A | p.Val845Ile | missense_variant | 18/35 | ENST00000344626.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCA4 | ENST00000646693.2 | c.2533G>A | p.Val845Ile | missense_variant | 18/36 | NM_001387283.1 | |||
SMARCA4 | ENST00000344626.10 | c.2533G>A | p.Val845Ile | missense_variant | 18/35 | 1 | NM_003072.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460412Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726364
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74374
ClinVar
Submissions by phenotype
Rhabdoid tumor predisposition syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 23, 2017 | 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. 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 tolerated, 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 SMARCA4-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with isoleucine at codon 845 of the SMARCA4 protein (p.Val845Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at