rs149037185
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_033305.3(VPS13A):āc.1758T>Cā(p.Ala586=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,613,638 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0020 ( 2 hom., cov: 32)
Exomes š: 0.0024 ( 11 hom. )
Consequence
VPS13A
NM_033305.3 synonymous
NM_033305.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.244
Genes affected
VPS13A (HGNC:1908): (vacuolar protein sorting 13 homolog A) The protein encoded by this gene may control steps in the cycling of proteins through the trans-Golgi network to endosomes, lysosomes and the plasma membrane. Mutations in this gene cause the autosomal recessive disorder, chorea-acanthocytosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
Variant 9-77238164-T-C is Benign according to our data. Variant chr9-77238164-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 367357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-77238164-T-C is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00196 (298/152328) while in subpopulation AMR AF= 0.00314 (48/15300). AF 95% confidence interval is 0.00272. There are 2 homozygotes in gnomad4. There are 135 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS13A | NM_033305.3 | c.1758T>C | p.Ala586= | synonymous_variant | 18/72 | ENST00000360280.8 | |
VPS13A | NM_001018037.2 | c.1758T>C | p.Ala586= | synonymous_variant | 18/71 | ||
VPS13A | NM_015186.4 | c.1758T>C | p.Ala586= | synonymous_variant | 18/69 | ||
VPS13A | NM_001018038.3 | c.1758T>C | p.Ala586= | synonymous_variant | 18/69 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS13A | ENST00000360280.8 | c.1758T>C | p.Ala586= | synonymous_variant | 18/72 | 1 | NM_033305.3 | P4 | |
VPS13A | ENST00000376636.7 | c.1758T>C | p.Ala586= | synonymous_variant | 18/71 | 1 | |||
VPS13A | ENST00000643348.1 | c.1758T>C | p.Ala586= | synonymous_variant | 18/69 | ||||
VPS13A | ENST00000645632.1 | c.1758T>C | p.Ala586= | synonymous_variant | 18/69 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00196 AC: 298AN: 152210Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00194 AC: 487AN: 250934Hom.: 1 AF XY: 0.00205 AC XY: 278AN XY: 135738
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GnomAD4 exome AF: 0.00241 AC: 3515AN: 1461310Hom.: 11 Cov.: 32 AF XY: 0.00235 AC XY: 1709AN XY: 726978
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GnomAD4 genome ? AF: 0.00196 AC: 298AN: 152328Hom.: 2 Cov.: 32 AF XY: 0.00181 AC XY: 135AN XY: 74494
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:5
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 29, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | VPS13A: BP4, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Chorea-acanthocytosis Benign:4
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 22, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
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 | Fulgent Genetics, Fulgent Genetics | Nov 17, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 05, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at