rs41289967
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_033305.3(VPS13A):c.4642G>A(p.Glu1548Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,608,202 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_033305.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VPS13A | NM_033305.3 | c.4642G>A | p.Glu1548Lys | missense_variant | 39/72 | ENST00000360280.8 | NP_150648.2 | |
VPS13A | NM_001018037.2 | c.4525G>A | p.Glu1509Lys | missense_variant | 38/71 | NP_001018047.1 | ||
VPS13A | NM_015186.4 | c.4642G>A | p.Glu1548Lys | missense_variant | 39/69 | NP_056001.1 | ||
VPS13A | NM_001018038.3 | c.4642G>A | p.Glu1548Lys | missense_variant | 39/69 | NP_001018048.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VPS13A | ENST00000360280.8 | c.4642G>A | p.Glu1548Lys | missense_variant | 39/72 | 1 | NM_033305.3 | ENSP00000353422.3 |
Frequencies
GnomAD3 genomes AF: 0.00211 AC: 320AN: 151584Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00206 AC: 514AN: 249830Hom.: 1 AF XY: 0.00216 AC XY: 292AN XY: 135316
GnomAD4 exome AF: 0.00253 AC: 3687AN: 1456500Hom.: 12 Cov.: 30 AF XY: 0.00247 AC XY: 1791AN XY: 724712
GnomAD4 genome AF: 0.00211 AC: 320AN: 151702Hom.: 2 Cov.: 32 AF XY: 0.00200 AC XY: 148AN XY: 74120
ClinVar
Submissions by phenotype
not provided Benign:6
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 28, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | VPS13A: BP4, BS2 - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Chorea-acanthocytosis Benign:3
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 05, 2020 | - - |
VPS13A-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 01, 2021 | 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