rs201861727
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_002506.3(NGF):c.173C>T(p.Ala58Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000501 in 1,614,214 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A58A) has been classified as Likely benign.
Frequency
Consequence
NM_002506.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NGF | NM_002506.3 | c.173C>T | p.Ala58Val | missense_variant | 3/3 | ENST00000369512.3 | |
NGF-AS1 | NR_157569.1 | n.207+3383G>A | intron_variant, non_coding_transcript_variant | ||||
NGF | XM_011541518.3 | c.338C>T | p.Ala113Val | missense_variant | 3/3 | ||
NGF | XM_006710663.4 | c.173C>T | p.Ala58Val | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NGF | ENST00000369512.3 | c.173C>T | p.Ala58Val | missense_variant | 3/3 | 1 | NM_002506.3 | P1 | |
NGF-AS1 | ENST00000425449.1 | n.207+3383G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000328 AC: 50AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00113 AC: 283AN: 251342Hom.: 2 AF XY: 0.00132 AC XY: 180AN XY: 135882
GnomAD4 exome AF: 0.000519 AC: 758AN: 1461876Hom.: 14 Cov.: 30 AF XY: 0.000722 AC XY: 525AN XY: 727244
GnomAD4 genome ? AF: 0.000328 AC: 50AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.000483 AC XY: 36AN XY: 74476
ClinVar
Submissions by phenotype
Congenital sensory neuropathy with selective loss of small myelinated fibers Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 09, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
NGF-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 19, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at