X-54440783-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_058163.3(TSR2):c.172+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000941 in 1,062,273 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_058163.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TSR2 | NM_058163.3 | c.172+3G>A | splice_region_variant, intron_variant | Intron 2 of 4 | ENST00000375151.5 | NP_477511.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 exomes AF: 0.00000691 AC: 1AN: 144719Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 38251
GnomAD4 exome AF: 9.41e-7 AC: 1AN: 1062273Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 334503
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change falls in intron 2 of the TSR2 gene. It does not directly change the encoded amino acid sequence of the TSR2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with TSR2-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at