chr16-46660126-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_018206.6(VPS35):c.*346G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000553 in 193,658 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00061 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00038 ( 0 hom. )
Consequence
VPS35
NM_018206.6 3_prime_UTR
NM_018206.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.368
Genes affected
VPS35 (HGNC:13487): (VPS35 retromer complex component) This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 16-46660126-C-T is Benign according to our data. Variant chr16-46660126-C-T is described in ClinVar as [Benign]. Clinvar id is 319272.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 87 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS35 | NM_018206.6 | c.*346G>A | 3_prime_UTR_variant | 17/17 | ENST00000299138.12 | ||
VPS35 | XM_005256045.4 | c.*346G>A | 3_prime_UTR_variant | 15/15 | |||
VPS35 | XM_011523227.4 | c.*346G>A | 3_prime_UTR_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS35 | ENST00000299138.12 | c.*346G>A | 3_prime_UTR_variant | 17/17 | 1 | NM_018206.6 | P1 | ||
VPS35 | ENST00000568784.6 | c.*3407G>A | 3_prime_UTR_variant, NMD_transcript_variant | 17/17 | 1 | ||||
VPS35 | ENST00000647959.1 | c.*2800G>A | 3_prime_UTR_variant, NMD_transcript_variant | 18/18 |
Frequencies
GnomAD3 genomes ? AF: 0.000615 AC: 87AN: 141418Hom.: 1 Cov.: 32
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GnomAD4 exome AF: 0.000383 AC: 20AN: 52182Hom.: 0 Cov.: 0 AF XY: 0.000446 AC XY: 12AN XY: 26878
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GnomAD4 genome ? AF: 0.000615 AC: 87AN: 141476Hom.: 1 Cov.: 32 AF XY: 0.000528 AC XY: 36AN XY: 68172
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Parkinson disease 17 Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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