rs202090510
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_033305.3(VPS13A):c.398C>T(p.Pro133Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00022 in 1,610,904 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P133P) has been classified as Likely benign.
Frequency
Consequence
NM_033305.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS13A | NM_033305.3 | c.398C>T | p.Pro133Leu | missense_variant | 6/72 | ENST00000360280.8 | |
VPS13A | NM_001018037.2 | c.398C>T | p.Pro133Leu | missense_variant | 6/71 | ||
VPS13A | NM_015186.4 | c.398C>T | p.Pro133Leu | missense_variant | 6/69 | ||
VPS13A | NM_001018038.3 | c.398C>T | p.Pro133Leu | missense_variant | 6/69 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13A | ENST00000360280.8 | c.398C>T | p.Pro133Leu | missense_variant | 6/72 | 1 | NM_033305.3 | P4 | |
VPS13A | ENST00000376636.7 | c.398C>T | p.Pro133Leu | missense_variant | 6/71 | 1 | |||
VPS13A | ENST00000643348.1 | c.398C>T | p.Pro133Leu | missense_variant | 6/69 | ||||
VPS13A | ENST00000645632.1 | c.398C>T | p.Pro133Leu | missense_variant | 6/69 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 151834Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000276 AC: 69AN: 249580Hom.: 0 AF XY: 0.000244 AC XY: 33AN XY: 134974
GnomAD4 exome AF: 0.000232 AC: 339AN: 1458952Hom.: 1 Cov.: 30 AF XY: 0.000207 AC XY: 150AN XY: 725804
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 151952Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74246
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 07, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 133 of the VPS13A protein (p.Pro133Leu). This variant is present in population databases (rs202090510, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with VPS13A-related conditions. ClinVar contains an entry for this variant (Variation ID: 448860). 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. 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