1-115286234-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_002506.3(NGF):c.562G>A(p.Gly188Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000421 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 same amino acid change has been previously reported as Uncertain significancein ClinVar.
Frequency
Consequence
NM_002506.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NGF | NM_002506.3 | c.562G>A | p.Gly188Arg | missense_variant | 3/3 | ENST00000369512.3 | |
NGF-AS1 | NR_157569.1 | n.207+2994C>T | intron_variant, non_coding_transcript_variant | ||||
NGF | XM_011541518.3 | c.727G>A | p.Gly243Arg | missense_variant | 3/3 | ||
NGF | XM_006710663.4 | c.562G>A | p.Gly188Arg | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NGF | ENST00000369512.3 | c.562G>A | p.Gly188Arg | missense_variant | 3/3 | 1 | NM_002506.3 | P1 | |
NGF-AS1 | ENST00000425449.1 | n.207+2994C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251484Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461890Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30AN XY: 727248
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74304
ClinVar
Submissions by phenotype
Congenital sensory neuropathy with selective loss of small myelinated fibers Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 19, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 24, 2022 | 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 0.006%). 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: 246559). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | Oct 15, 2019 | The p.G188R variant (also known as c.562G>A), located in coding exon 1 of the NGF gene, results from a G to A substitution at nucleotide position 562. The glycine at codon 188 is replaced by arginine, an amino acid with dissimilar properties. This nucleotide position is highly conserved in available vertebrate species. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 29, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at