rs1555608659
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001042492.3(NF1):āc.614A>Gā(p.Lys205Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,220 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. K205E) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.614A>G | p.Lys205Arg | missense_variant | 6/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.614A>G | p.Lys205Arg | missense_variant | 6/57 | ||
NF1 | NM_001128147.3 | c.614A>G | p.Lys205Arg | missense_variant | 6/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.614A>G | p.Lys205Arg | missense_variant | 6/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461220Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726900
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 05, 2023 | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 205 of the NF1 protein (p.Lys205Arg). 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: 480207). 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 expected to disrupt 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 | - - |
Juvenile myelomonocytic leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 26, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 23, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2023 | The p.K205R variant (also known as c.614A>G), located in coding exon 6 of the NF1 gene, results from an A to G substitution at nucleotide position 614. The lysine at codon 205 is replaced by arginine, 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