1-115286461-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002506.3(NGF):c.335C>A(p.Pro112His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. P112R) has been classified 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NGF | NM_002506.3 | c.335C>A | p.Pro112His | missense_variant | Exon 3 of 3 | ENST00000369512.3 | NP_002497.2 | |
NGF | XM_011541518.3 | c.500C>A | p.Pro167His | missense_variant | Exon 3 of 3 | XP_011539820.1 | ||
NGF | XM_006710663.4 | c.335C>A | p.Pro112His | missense_variant | Exon 2 of 2 | XP_006710726.1 | ||
NGF-AS1 | NR_157569.1 | n.207+3221G>T | intron_variant | Intron 1 of 1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152034Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250978Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135622
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461592Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727022
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152034Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74250
ClinVar
Submissions by phenotype
Congenital sensory neuropathy with selective loss of small myelinated fibers Uncertain:1
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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with NGF-related conditions. This variant is present in population databases (rs147763877, ExAC 0.003%). This sequence change replaces proline with histidine at codon 112 of the NGF protein (p.Pro112His). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and histidine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at