chr17-31260484-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP3
The NM_001042492.3(NF1):c.4546G>C(p.Glu1516Gln) variant causes a missense 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1516D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001042492.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.4546G>C | p.Glu1516Gln | missense_variant | 34/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.4483G>C | p.Glu1495Gln | missense_variant | 33/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.4546G>C | p.Glu1516Gln | missense_variant | 34/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 13, 2014 | The p.E1516Q variant (also known as c.4546G>C), located in coding exon 34 of the NF1 gene, results from a G to C substitution at nucleotide position 4546. The glutamic acid at codon 1516 is replaced by glutamine, an amino acid with highly similar 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.<span style="background-color: initial;">To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 11000 alleles tested) in our clinical cohort.<span style="background-color: initial;"><span style="background-color: initial;">This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be possibly damaging and deleterious by PolyPhen and SIFT <em style="background-color: initial;">in silico<span style="background-color: initial;"> analyses, respectively. <span style="background-color: initial;">Since supporting evidence is limited at this time, the clinical significance of<span style="background-color: initial;">p.E1516Q<span style="background-color: initial;">remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at