rs267606609
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PP2PP5
The NM_001042492.3(NF1):c.945_946delinsAA(p.Leu316Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
NF1
NM_001042492.3 missense
NM_001042492.3 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.33
Genes affected
NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 14 uncertain in NM_001042492.3
PP2
?
Missense variant where missense usually causes diseases, NF1
PP5
?
Variant 17-31200478-GC-AA is Pathogenic according to our data. Variant chr17-31200478-GC-AA is described in ClinVar as [Pathogenic]. Clinvar id is 366.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.945_946delinsAA | p.Leu316Met | missense_variant | 9/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.945_946delinsAA | p.Leu316Met | missense_variant | 9/57 | ||
NF1 | NM_001128147.3 | c.945_946delinsAA | p.Leu316Met | missense_variant | 9/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.945_946delinsAA | p.Leu316Met | missense_variant | 9/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Neurofibromatosis, type 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2003 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at