rs149694033
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_033305.3(VPS13A):c.5884C>T(p.Arg1962Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 1,613,306 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_033305.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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VPS13A | NM_033305.3 | c.5884C>T | p.Arg1962Cys | missense_variant | Exon 45 of 72 | ENST00000360280.8 | NP_150648.2 | |
VPS13A | NM_001018037.2 | c.5767C>T | p.Arg1923Cys | missense_variant | Exon 44 of 71 | NP_001018047.1 | ||
VPS13A | NM_015186.4 | c.5884C>T | p.Arg1962Cys | missense_variant | Exon 45 of 69 | NP_056001.1 | ||
VPS13A | NM_001018038.3 | c.5884C>T | p.Arg1962Cys | missense_variant | Exon 45 of 69 | NP_001018048.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00393 AC: 598AN: 152042Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.00362 AC: 907AN: 250868Hom.: 3 AF XY: 0.00358 AC XY: 485AN XY: 135582
GnomAD4 exome AF: 0.00506 AC: 7394AN: 1461146Hom.: 24 Cov.: 30 AF XY: 0.00491 AC XY: 3566AN XY: 726856
GnomAD4 genome AF: 0.00392 AC: 597AN: 152160Hom.: 3 Cov.: 32 AF XY: 0.00383 AC XY: 285AN XY: 74378
ClinVar
Submissions by phenotype
not provided Benign:6
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VPS13A: BP4, BS2 -
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Chorea-acanthocytosis Uncertain:2Benign:3
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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
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not specified Benign:1
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VPS13A-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at