rs782749176
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_003334.4(UBA1):āc.2626C>Gā(p.Pro876Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,209,898 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
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.2626C>G | p.Pro876Ala | missense_variant | 22/26 | ENST00000335972.11 | |
LOC105373194 | XR_949047.4 | n.277+4163G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBA1 | ENST00000335972.11 | c.2626C>G | p.Pro876Ala | missense_variant | 22/26 | 1 | NM_003334.4 | P1 | |
UBA1 | ENST00000377351.8 | c.2626C>G | p.Pro876Ala | missense_variant | 22/26 | 1 | P1 | ||
UBA1 | ENST00000377269.3 | c.970C>G | p.Pro324Ala | missense_variant | 6/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000893 AC: 1AN: 112017Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34153
GnomAD4 exome AF: 0.00000182 AC: 2AN: 1097881Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1AN XY: 363237
GnomAD4 genome ? AF: 0.00000893 AC: 1AN: 112017Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34153
ClinVar
Submissions by phenotype
Infantile-onset X-linked spinal muscular atrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2022 | 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. ClinVar contains an entry for this variant (Variation ID: 582593). This variant has not been reported in the literature in individuals affected with UBA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 876 of the UBA1 protein (p.Pro876Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at