17-31249019-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The NM_001042492.3(NF1):c.4010G>T(p.Arg1337Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,002 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. R1337Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001042492.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.4010G>T | p.Arg1337Leu | missense_variant | 30/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.4010G>T | p.Arg1337Leu | missense_variant | 30/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.4010G>T | p.Arg1337Leu | missense_variant | 30/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152002Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152002Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74248
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 26, 2016 | This variant is denoted NF1 c.4010G>T at the cDNA level, p.Arg1337Leu (R1337L) at the protein level, and results in the change of an Arginine to a Leucine (CGG>CTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Arg1337Leu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Arginine and Leucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. NF1 Arg1337Leu occurs at a position that is conserved in mammals and is located within the Ras-GAP domain (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether NF1 Arg1337Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. - |
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 22, 2020 | The p.R1337L variant (also known as c.4010G>T), located in coding exon 30 of the NF1 gene, results from a G to T substitution at nucleotide position 4010. The arginine at codon 1337 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well 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