17-31219084-C-G
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001042492.3(NF1):c.1607C>G(p.Ser536*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001042492.3 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.1607C>G | p.Ser536* | stop_gained | Exon 14 of 58 | ENST00000358273.9 | NP_001035957.1 | |
NF1 | NM_000267.3 | c.1607C>G | p.Ser536* | stop_gained | Exon 14 of 57 | NP_000258.1 | ||
NF1 | NM_001128147.3 | c.1607C>G | p.Ser536* | stop_gained | Exon 14 of 15 | NP_001121619.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Pathogenic:3
- -
- -
This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with neurofibromatosis type 1 (PMID: 30530636). ClinVar contains an entry for this variant (Variation ID: 547597). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Ser536*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at