rs387906709
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PM5PP3PP5_Moderate
The NM_013444.4(UBQLN2):c.1490C>A(p.Pro497His) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P497L) has been classified as Uncertain significance.
Frequency
Consequence
NM_013444.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBQLN2 | NM_013444.4 | c.1490C>A | p.Pro497His | missense_variant | 1/1 | ENST00000338222.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBQLN2 | ENST00000338222.7 | c.1490C>A | p.Pro497His | missense_variant | 1/1 | NM_013444.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 24
ClinVar
Submissions by phenotype
Amyotrophic lateral sclerosis type 15 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 23, 2021 | This sequence change replaces proline with histidine at codon 497 of the UBQLN2 protein (p.Pro497His). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and histidine. This variant has been observed in individuals with amyotrophic lateral sclerosis (PMID: 21857683, 30348461). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 29950). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects UBQLN2 protein function (PMID: 21857683, 24215460, 25398946). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (ExAC no frequency). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 21, 2011 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at