rs876658642
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001042492.3(NF1):c.1310T>A(p.Val437Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.1310T>A | p.Val437Asp | missense_variant | Exon 12 of 58 | ENST00000358273.9 | NP_001035957.1 | |
NF1 | NM_000267.3 | c.1310T>A | p.Val437Asp | missense_variant | Exon 12 of 57 | NP_000258.1 | ||
NF1 | NM_001128147.3 | c.1310T>A | p.Val437Asp | missense_variant | Exon 12 of 15 | NP_001121619.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Uncertain:1Benign:1
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Juvenile myelomonocytic leukemia Uncertain:1
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not provided Uncertain:1
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates 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
The c.1310T>A (p.V437D) alteration is located in exon 12 (coding exon 12) of the NF1 gene. This alteration results from a T to A substitution at nucleotide position 1310, causing the valine (V) at amino acid position 437 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Hereditary cancer-predisposing syndrome Uncertain:1
Thep.V437D variant (also known as c.1310T>A), located in coding exon 12 of theNF1 gene, results from a T to A substitution at nucleotide position 1310. The valine at codon 437 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.004% (greater than 55000 alleles tested) in our clinical cohort. Based on sequence alignment, this amino acid position is highly conserved through reptiles. In addition, this alteration is predicted to be benign and tolerated by PolyPhen and SIFTin silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.V437D remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at