17-31229871-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001042492.3(NF1):c.2887C>T(p.Gln963Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. 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 Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Q963Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001042492.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.2887C>T | p.Gln963Ter | stop_gained | 22/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.2887C>T | p.Gln963Ter | stop_gained | 22/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.2887C>T | p.Gln963Ter | stop_gained | 22/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1459506Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726064
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | DASA | Nov 03, 2022 | The c.2887C>T;p.(Gln963*) variant creates a premature translational stop signal in the NF1 gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 233495; PMID: 10862084; 31370276) - PS4. This variant is not present in population databases (rs876660444, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 02, 2022 | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln963*) 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). This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 1 (PMID: 10862084). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 233495). - |
Pathogenic, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Malignant tumor of urinary bladder Pathogenic:1
Pathogenic, no assertion criteria provided | research | Laboratory of Urology, Hospital Clinic de Barcelona | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 30, 2019 | - - |
Gastric cancer Pathogenic:1
Pathogenic, no assertion criteria provided | research | Laboratory for Genotyping Development, RIKEN | Jul 01, 2021 | - - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 18, 2015 | The p.Q963* pathogenic mutation (also known as c.2887C>T), located in coding exon 22 of the NF1 gene, results from a C to T substitution at nucleotide position 2887. This changes the amino acid from a glutamine to a stop codon within coding exon 22. This mutation was reported in an individual who fulfilled NIH consensus criteria for neurofibromatosistype1 (Messiaen LM, et al. Hum. Mutat. 2000;15(6):541-55). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at