rs1553234811
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002506.3(NGF):c.133G>A(p.Asp45Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NGF | NM_002506.3 | c.133G>A | p.Asp45Asn | missense_variant | 3/3 | ENST00000369512.3 | |
NGF-AS1 | NR_157569.1 | n.207+3423C>T | intron_variant, non_coding_transcript_variant | ||||
NGF | XM_011541518.3 | c.298G>A | p.Asp100Asn | missense_variant | 3/3 | ||
NGF | XM_006710663.4 | c.133G>A | p.Asp45Asn | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NGF | ENST00000369512.3 | c.133G>A | p.Asp45Asn | missense_variant | 3/3 | 1 | NM_002506.3 | P1 | |
NGF-AS1 | ENST00000425449.1 | n.207+3423C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461880Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727242
GnomAD4 genome ? Cov.: 32
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 | Sep 15, 2018 | In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an NGF-related disease. This sequence change replaces aspartic acid with asparagine at codon 45 of the NGF protein (p.Asp45Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 02, 2020 | The p.D45N variant (also known as c.133G>A), located in coding exon 1 of the NGF gene, results from a G to A substitution at nucleotide position 133. The aspartic acid at codon 45 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is 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