9-77339827-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_033305.3(VPS13A):c.6690C>T(p.Asp2230Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000812 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00069 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00082 ( 0 hom. )
Consequence
VPS13A
NM_033305.3 synonymous
NM_033305.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.77
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 -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 9-77339827-C-T is Benign according to our data. Variant chr9-77339827-C-T is described in ClinVar as [Benign]. Clinvar id is 448869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-77339827-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1.77 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| VPS13A | NM_033305.3 | c.6690C>T | p.Asp2230Asp | synonymous_variant | Exon 48 of 72 | ENST00000360280.8 | NP_150648.2 | |
| VPS13A | NM_001018037.2 | c.6573C>T | p.Asp2191Asp | synonymous_variant | Exon 47 of 71 | NP_001018047.1 | ||
| VPS13A | NM_015186.4 | c.6690C>T | p.Asp2230Asp | synonymous_variant | Exon 48 of 69 | NP_056001.1 | ||
| VPS13A | NM_001018038.3 | c.6690C>T | p.Asp2230Asp | synonymous_variant | Exon 48 of 69 | NP_001018048.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| VPS13A | ENST00000360280.8 | c.6690C>T | p.Asp2230Asp | synonymous_variant | Exon 48 of 72 | 1 | NM_033305.3 | ENSP00000353422.3 | ||
| VPS13A | ENST00000376636.7 | c.6573C>T | p.Asp2191Asp | synonymous_variant | Exon 47 of 71 | 1 | ENSP00000365823.3 | |||
| VPS13A | ENST00000643348.1 | c.6690C>T | p.Asp2230Asp | synonymous_variant | Exon 48 of 69 | ENSP00000493592.1 | ||||
| VPS13A | ENST00000645632.1 | c.6690C>T | p.Asp2230Asp | synonymous_variant | Exon 48 of 69 | ENSP00000496361.1 |
Frequencies
GnomAD3 genomes 0.000690 AC: 105AN: 152102Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000794 AC: 199AN: 250532Hom.: 0 AF XY: 0.000768 AC XY: 104AN XY: 135394
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GnomAD4 exome AF: 0.000824 AC: 1205AN: 1461702Hom.: 0 Cov.: 34 AF XY: 0.000807 AC XY: 587AN XY: 727142
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GnomAD4 genome 0.000690 AC: 105AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.000712 AC XY: 53AN XY: 74414
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Apr 23, 2019
Athena Diagnostics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Jan 23, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Chorea-acanthocytosis Benign:1
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
VPS13A-related disorder Benign:1
Sep 13, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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
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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