chrX-56564841-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_013444.4(UBQLN2):c.968C>T(p.Pro323Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,097,963 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P323P) has been classified as Likely benign.
Frequency
Consequence
NM_013444.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome AF: 0.0000100 AC: 11AN: 1097963Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 2AN XY: 363317
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Amyotrophic lateral sclerosis type 15 Uncertain:1
This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 323 of the UBQLN2 protein (p.Pro323Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant has not been reported in the literature in individuals with UBQLN2-related disease. 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at