rs758166016
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_002506.3(NGF):c.539G>A(p.Arg180Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002506.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NGF | NM_002506.3 | c.539G>A | p.Arg180Gln | missense_variant | 3/3 | ENST00000369512.3 | |
NGF-AS1 | NR_157569.1 | n.207+3017C>T | intron_variant, non_coding_transcript_variant | ||||
NGF | XM_011541518.3 | c.704G>A | p.Arg235Gln | missense_variant | 3/3 | ||
NGF | XM_006710663.4 | c.539G>A | p.Arg180Gln | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NGF | ENST00000369512.3 | c.539G>A | p.Arg180Gln | missense_variant | 3/3 | 1 | NM_002506.3 | P1 | |
NGF-AS1 | ENST00000425449.1 | n.207+3017C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152118Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251492Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135920
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461892Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727246
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74298
ClinVar
Submissions by phenotype
Congenital sensory neuropathy with selective loss of small myelinated fibers Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 24, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 180 of the NGF protein (p.Arg180Gln). This variant is present in population databases (rs758166016, gnomAD 0.01%). 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: 576877). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2020 | The p.R180Q variant (also known as c.539G>A), located in coding exon 1 of the NGF gene, results from a G to A substitution at nucleotide position 539. The arginine at codon 180 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at