rs768536854
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003079.5(SMARCE1):c.932C>T(p.Ala311Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A311A) has been classified as Likely benign.
Frequency
Consequence
NM_003079.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCE1 | NM_003079.5 | c.932C>T | p.Ala311Val | missense_variant | 10/11 | ENST00000348513.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCE1 | ENST00000348513.12 | c.932C>T | p.Ala311Val | missense_variant | 10/11 | 1 | NM_003079.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251342Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135838
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461822Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727218
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Familial meningioma Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 25, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2023 | This variant has not been reported in the literature in individuals affected with SMARCE1-related conditions. This variant is present in population databases (rs768536854, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 311 of the SMARCE1 protein (p.Ala311Val). ClinVar contains an entry for this variant (Variation ID: 532236). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SMARCE1 protein function. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 15, 2021 | The p.A311V variant (also known as c.932C>T), located in coding exon 9 of the SMARCE1 gene, results from a C to T substitution at nucleotide position 932. The alanine at codon 311 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at