rs750488772
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1PM2PP2BP4_Moderate
The NM_001042492.3(NF1):āc.2856A>Cā(p.Leu952Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,428 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L952L) has been classified as Likely benign.
Frequency
Consequence
NM_001042492.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.2856A>C | p.Leu952Phe | missense_variant | 22/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.2856A>C | p.Leu952Phe | missense_variant | 22/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.2856A>C | p.Leu952Phe | missense_variant | 22/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459428Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726022
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 952 of the NF1 protein (p.Leu952Phe). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 481933). 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. - |
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 25, 2023 | The p.L952F variant (also known as c.2856A>C), located in coding exon 22 of the NF1 gene, results from an A to C substitution at nucleotide position 2856. The leucine at codon 952 is replaced by phenylalanine, 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