1-115286234-C-G
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_002506.3(NGF):c.562G>C(p.Gly188Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.
Frequency
Consequence
NM_002506.3 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NGF | NM_002506.3 | c.562G>C | p.Gly188Arg | missense_variant | Exon 3 of 3 | ENST00000369512.3 | NP_002497.2 | |
NGF | NM_001437545.1 | c.562G>C | p.Gly188Arg | missense_variant | Exon 2 of 2 | NP_001424474.1 | ||
NGF | XM_011541518.3 | c.727G>C | p.Gly243Arg | missense_variant | Exon 3 of 3 | XP_011539820.1 | ||
NGF-AS1 | NR_157569.1 | n.207+2994C>G | intron_variant | Intron 1 of 1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000795 AC: 2AN: 251484 AF XY: 0.00000736 show subpopulations
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461890Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727248 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74304 show subpopulations
ClinVar
Submissions by phenotype
Congenital sensory neuropathy with selective loss of small myelinated fibers Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 188 of the NGF protein (p.Gly188Arg). This variant is present in population databases (rs760753923, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with NGF-related conditions. ClinVar contains an entry for this variant (Variation ID: 834309). 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 disruptive. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at