chr17-40628802-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003079.5(SMARCE1):c.1219G>A(p.Asp407Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. D407G) has been classified as Uncertain significance.
Frequency
Consequence
NM_003079.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCE1 | NM_003079.5 | c.1219G>A | p.Asp407Asn | missense_variant | 11/11 | ENST00000348513.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCE1 | ENST00000348513.12 | c.1219G>A | p.Asp407Asn | missense_variant | 11/11 | 1 | NM_003079.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250662Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135480
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460504Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726594
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial meningioma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 29, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 407 of the SMARCE1 protein (p.Asp407Asn). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SMARCE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1023064). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 24, 2022 | The p.D407N variant (also known as c.1219G>A), located in coding exon 10 of the SMARCE1 gene, results from a G to A substitution at nucleotide position 1219. The aspartic acid at codon 407 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well 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