X-47206074-C-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003334.4(UBA1):āc.1702C>Gā(p.Leu568Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,203,705 control chromosomes in the GnomAD database, including 55 homozygotes. There are 1,397 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_003334.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UBA1 | NM_003334.4 | c.1702C>G | p.Leu568Val | missense_variant | Exon 15 of 26 | ENST00000335972.11 | NP_003325.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
UBA1 | ENST00000335972.11 | c.1702C>G | p.Leu568Val | missense_variant | Exon 15 of 26 | 1 | NM_003334.4 | ENSP00000338413.6 | ||
UBA1 | ENST00000377351.8 | c.1702C>G | p.Leu568Val | missense_variant | Exon 15 of 26 | 1 | ENSP00000366568.4 | |||
UBA1 | ENST00000490869.1 | n.465-4C>G | splice_region_variant, intron_variant | Intron 4 of 5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00410 AC: 458AN: 111825Hom.: 4 Cov.: 24 AF XY: 0.00509 AC XY: 173AN XY: 34011
GnomAD3 exomes AF: 0.00782 AC: 1306AN: 167034Hom.: 18 AF XY: 0.00702 AC XY: 379AN XY: 54020
GnomAD4 exome AF: 0.00345 AC: 3772AN: 1091826Hom.: 51 Cov.: 31 AF XY: 0.00342 AC XY: 1225AN XY: 358234
GnomAD4 genome AF: 0.00408 AC: 456AN: 111879Hom.: 4 Cov.: 24 AF XY: 0.00505 AC XY: 172AN XY: 34075
ClinVar
Submissions by phenotype
not specified Benign:2
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Infantile-onset X-linked spinal muscular atrophy Benign:2
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
UBA1-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
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Infantile-onset X-linked spinal muscular atrophy;C5435753:VEXAS syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at