17-31235713-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM1PP2BS2_Supporting
The NM_001042492.3(NF1):c.3811A>G(p.Met1271Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251298Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135808
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461838Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727224
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152308Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74484
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Uncertain:1Benign:1
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Neurofibromatosis, type 1;C0349639:Juvenile myelomonocytic leukemia;C0553586:Café-au-lait macules with pulmonary stenosis;C1834235:Neurofibromatosis, familial spinal;C2931482:Neurofibromatosis-Noonan syndrome Uncertain:1
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not provided Uncertain:1
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; This variant is associated with the following publications: (PMID: 25486365, 22807134) -
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Uncertain:1
The p.M1271V variant (also known as c.3811A>G), located in coding exon 28 of the NF1 gene, results from an A to G substitution at nucleotide position 3811. The methionine at codon 1271 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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