15-61856283-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020821.3(VPS13C):c.11076+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,612,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_020821.3 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS13C | NM_020821.3 | c.11076+3A>G | splice_region_variant, intron_variant | Intron 83 of 84 | ENST00000644861.2 | NP_065872.1 | ||
VPS13C | NM_017684.5 | c.10947+3A>G | splice_region_variant, intron_variant | Intron 81 of 82 | NP_060154.3 | |||
LOC124903501 | XR_007064668.1 | n.159+6811T>C | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000720 AC: 18AN: 250162Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135222
GnomAD4 exome AF: 0.000103 AC: 151AN: 1460584Hom.: 0 Cov.: 30 AF XY: 0.0000950 AC XY: 69AN XY: 726604
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 25, 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. 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 may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with VPS13C-related conditions. This variant is present in population databases (rs368174588, gnomAD 0.02%). This sequence change falls in intron 83 of the VPS13C gene. It does not directly change the encoded amino acid sequence of the VPS13C protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at