rs1556788657
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_003334.4(UBA1):c.1048C>T(p.Arg350Cys) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R350H) has been classified as Likely benign.
Frequency
Consequence
NM_003334.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBA1 | NM_003334.4 | c.1048C>T | p.Arg350Cys | missense_variant | 10/26 | ENST00000335972.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBA1 | ENST00000335972.11 | c.1048C>T | p.Arg350Cys | missense_variant | 10/26 | 1 | NM_003334.4 | P1 | |
UBA1 | ENST00000377351.8 | c.1048C>T | p.Arg350Cys | missense_variant | 10/26 | 1 | P1 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.20e-7 AC: 1AN: 1087260Hom.: 0 Cov.: 33 AF XY: 0.00000282 AC XY: 1AN XY: 355206
GnomAD4 genome Cov.: 24
ClinVar
Submissions by phenotype
Infantile-onset X-linked spinal muscular atrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 02, 2017 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with UBA1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 350 of the UBA1 protein (p.Arg350Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at