15-61856365-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020821.3(VPS13C):c.10997G>A(p.Cys3666Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_020821.3 missense
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS13C | NM_020821.3 | c.10997G>A | p.Cys3666Tyr | missense_variant | 83/85 | ENST00000644861.2 | NP_065872.1 | |
LOC124903501 | XR_007064668.1 | n.159+6893C>T | intron_variant, non_coding_transcript_variant | |||||
VPS13C | NM_017684.5 | c.10868G>A | p.Cys3623Tyr | missense_variant | 81/83 | NP_060154.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS13C | ENST00000644861.2 | c.10997G>A | p.Cys3666Tyr | missense_variant | 83/85 | NM_020821.3 | ENSP00000493560 | P3 | ||
ENST00000642740.1 | n.172+6893C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250682Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135502
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461138Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726882
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 21, 2021 | 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. This variant has not been reported in the literature in individuals affected with VPS13C-related conditions. This variant is present in population databases (rs762264051, gnomAD 0.01%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 3666 of the VPS13C protein (p.Cys3666Tyr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at