rs199474769
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001042492.3(NF1):c.1178A>G(p.His393Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. H393D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001042492.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.1178A>G | p.His393Arg | missense_variant | 10/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.1178A>G | p.His393Arg | missense_variant | 10/57 | ||
NF1 | NM_001128147.3 | c.1178A>G | p.His393Arg | missense_variant | 10/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.1178A>G | p.His393Arg | missense_variant | 10/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251346Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135832
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461788Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727186
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 393 of the NF1 protein (p.His393Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at