X-56565347-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_013444.4(UBQLN2):c.1474G>T(p.Val492Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign 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_013444.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBQLN2 | NM_013444.4 | c.1474G>T | p.Val492Leu | missense_variant | 1/1 | ENST00000338222.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBQLN2 | ENST00000338222.7 | c.1474G>T | p.Val492Leu | missense_variant | 1/1 | NM_013444.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD3 exomes AF: 0.00000588 AC: 1AN: 169951Hom.: 0 AF XY: 0.0000175 AC XY: 1AN XY: 57205
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.14e-7 AC: 1AN: 1094225Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 1AN XY: 360047
GnomAD4 genome Cov.: 24
ClinVar
Submissions by phenotype
Amyotrophic lateral sclerosis type 15 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 07, 2021 | 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals with UBQLN2-related conditions. This variant is present in population databases (rs756653207, ExAC 0.01%). This sequence change replaces valine with leucine at codon 492 of the UBQLN2 protein (p.Val492Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at