chr17-31182630-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001042492.3(NF1):āc.853T>Gā(p.Ser285Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,744 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S285F) has been classified as Uncertain significance.
Frequency
Consequence
NM_001042492.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.853T>G | p.Ser285Ala | missense_variant | 8/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.853T>G | p.Ser285Ala | missense_variant | 8/57 | ||
NF1 | NM_001128147.3 | c.853T>G | p.Ser285Ala | missense_variant | 8/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.853T>G | p.Ser285Ala | missense_variant | 8/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461568Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727060
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2024 | This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 285 of the NF1 protein (p.Ser285Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 527593). 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 NF1 protein function with a negative predictive value of 95%. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 03, 2021 | The p.S285A variant (also known as c.853T>G), located in coding exon 8 of the NF1 gene, results from a T to G substitution at nucleotide position 853. The serine at codon 285 is replaced by alanine, an amino acid with 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