X-71290753-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_007363.5(NONO):c.116C>T(p.Pro39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000672 in 1,189,845 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_007363.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NONO | NM_007363.5 | c.116C>T | p.Pro39Leu | missense_variant | Exon 3 of 12 | ENST00000276079.13 | NP_031389.3 | |
NONO | NM_001145408.2 | c.116C>T | p.Pro39Leu | missense_variant | Exon 4 of 13 | NP_001138880.1 | ||
NONO | NM_001145409.2 | c.116C>T | p.Pro39Leu | missense_variant | Exon 2 of 11 | NP_001138881.1 | ||
NONO | NM_001145410.2 | c.-113-1026C>T | intron_variant | Intron 1 of 9 | NP_001138882.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000890 AC: 1AN: 112297Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34457
GnomAD3 exomes AF: 0.0000209 AC: 3AN: 143829Hom.: 0 AF XY: 0.0000251 AC XY: 1AN XY: 39815
GnomAD4 exome AF: 0.00000650 AC: 7AN: 1077496Hom.: 0 Cov.: 30 AF XY: 0.00000861 AC XY: 3AN XY: 348400
GnomAD4 genome AF: 0.00000890 AC: 1AN: 112349Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34519
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: NONO c.116C>T (p.Pro39Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.1e-05 in 143829 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.116C>T in individuals affected with X-Linked Mental Retardation, Syndromic 34 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -
See cases Uncertain:1
ACMG categories: PP1,PP2,BP1 -
not provided Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 39 of the NONO protein (p.Pro39Leu). This variant is present in population databases (rs755285551, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with NONO-related conditions. ClinVar contains an entry for this variant (Variation ID: 1704517). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt NONO protein function with a negative predictive value of 80%. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at