17-31159061-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM1PP2BP4
The NM_001042492.3(NF1):c.256A>G(p.Ile86Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,609,168 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. I86L) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.256A>G | p.Ile86Val | missense_variant | 3/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.256A>G | p.Ile86Val | missense_variant | 3/57 | ||
NF1 | NM_001128147.3 | c.256A>G | p.Ile86Val | missense_variant | 3/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.256A>G | p.Ile86Val | missense_variant | 3/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250962Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135710
GnomAD4 exome AF: 0.00000618 AC: 9AN: 1457000Hom.: 0 Cov.: 28 AF XY: 0.00000689 AC XY: 5AN XY: 725184
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jul 24, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 86 of the NF1 protein (p.Ile86Val). This variant is present in population databases (rs757057811, gnomAD 0.003%). 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: 579548). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NF1 protein function. 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 | Mar 19, 2021 | The p.I86V variant (also known as c.256A>G), located in coding exon 3 of the NF1 gene, results from an A to G substitution at nucleotide position 256. The isoleucine at codon 86 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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