rs1555614180
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001042492.3(NF1):c.2411del(p.Ala804ValfsTer17) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. A804A) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001042492.3 frameshift, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.2411del | p.Ala804ValfsTer17 | frameshift_variant, splice_region_variant | 21/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.2411del | p.Ala804ValfsTer17 | frameshift_variant, splice_region_variant | 21/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.2411del | p.Ala804ValfsTer17 | frameshift_variant, splice_region_variant | 21/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 25, 2017 | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This sequence change deletes 1 nucleotide from exon 21 of the NF1 mRNA (c.2411delC), causing a frameshift at codon 804. This creates a premature translational stop signal (p.Ala804Valfs*17) and is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at