rs1555605079
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_003079.5(SMARCE1):c.1148G>A(p.Ser383Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,808 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. S383G) has been classified as Uncertain significance.
Frequency
Consequence
NM_003079.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCE1 | NM_003079.5 | c.1148G>A | p.Ser383Asn | missense_variant | 11/11 | ENST00000348513.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCE1 | ENST00000348513.12 | c.1148G>A | p.Ser383Asn | missense_variant | 11/11 | 1 | NM_003079.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461608Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727122
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
Familial meningioma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2022 | This variant has not been reported in the literature in individuals affected with SMARCE1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 383 of the SMARCE1 protein (p.Ser383Asn). ClinVar contains an entry for this variant (Variation ID: 463420). 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 | Jul 26, 2023 | The p.S383N variant (also known as c.1148G>A), located in coding exon 10 of the SMARCE1 gene, results from a G to A substitution at nucleotide position 1148. The serine at codon 383 is replaced by asparagine, an amino acid with highly 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. Missense and in-frame variants in SMARCE1 are known to cause neurodevelopmental disorders; however, such associations with increased risk of meningiomas are exceedingly rare (Kosho T et al. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75; Smith JM et al. Nat Genet. 2013 Mar;45(3):295-8). Based on the supporting evidence, the association of this alteration with an increased risk of Coffin-Siris syndrome is unknown; however, the association of this alteration with an increased risk of meningiomas is unlikely. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at