GeneBe

rs369756092

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_018206.6(VPS35):​c.*282dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1696 hom., cov: 0)
Exomes 𝑓: 0.054 ( 154 hom. )
Failed GnomAD Quality Control

Consequence

VPS35
NM_018206.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.37

Publications

2 publications found
Variant links:
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]
VPS35 Gene-Disease associations (from GenCC):
  • Parkinson disease
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • Parkinson disease 17
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
  • hereditary late onset Parkinson disease
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • intellectual disability
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2
High Homozygotes in GnomAdExome4 at 154 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018206.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
VPS35
NM_018206.6
MANE Select
c.*282dupA
3_prime_UTR
Exon 17 of 17NP_060676.2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
VPS35
ENST00000299138.12
TSL:1 MANE Select
c.*282dupA
3_prime_UTR
Exon 17 of 17ENSP00000299138.7Q96QK1
VPS35
ENST00000568784.6
TSL:1
n.*3343dupA
non_coding_transcript_exon
Exon 17 of 17ENSP00000456274.2H3BRJ7
VPS35
ENST00000568784.6
TSL:1
n.*3343dupA
3_prime_UTR
Exon 17 of 17ENSP00000456274.2H3BRJ7

Frequencies

GnomAD3 genomes
AF:
0.128
AC:
11497
AN:
89564
Hom.:
1694
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.297
Gnomad AMI
AF:
0.0117
Gnomad AMR
AF:
0.0998
Gnomad ASJ
AF:
0.0466
Gnomad EAS
AF:
0.00528
Gnomad SAS
AF:
0.0344
Gnomad FIN
AF:
0.0862
Gnomad MID
AF:
0.0943
Gnomad NFE
AF:
0.0581
Gnomad OTH
AF:
0.0991
GnomAD4 exome
AF:
0.0539
AC:
460
AN:
8530
Hom.:
154
Cov.:
0
AF XY:
0.0490
AC XY:
214
AN XY:
4366
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0466
AC:
11
AN:
236
American (AMR)
AF:
0.0554
AC:
37
AN:
668
Ashkenazi Jewish (ASJ)
AF:
0.0524
AC:
11
AN:
210
East Asian (EAS)
AF:
0.0306
AC:
11
AN:
360
South Asian (SAS)
AF:
0.0182
AC:
24
AN:
1320
European-Finnish (FIN)
AF:
0.0767
AC:
27
AN:
352
Middle Eastern (MID)
AF:
0.0313
AC:
1
AN:
32
European-Non Finnish (NFE)
AF:
0.0654
AC:
319
AN:
4878
Other (OTH)
AF:
0.0401
AC:
19
AN:
474
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.352
Heterozygous variant carriers
0
11
22
34
45
56
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.128
AC:
11501
AN:
89578
Hom.:
1696
Cov.:
0
AF XY:
0.132
AC XY:
5280
AN XY:
39928
show subpopulations
African (AFR)
AF:
0.297
AC:
7665
AN:
25794
American (AMR)
AF:
0.0994
AC:
647
AN:
6506
Ashkenazi Jewish (ASJ)
AF:
0.0466
AC:
119
AN:
2556
East Asian (EAS)
AF:
0.00529
AC:
12
AN:
2268
South Asian (SAS)
AF:
0.0331
AC:
71
AN:
2144
European-Finnish (FIN)
AF:
0.0862
AC:
122
AN:
1416
Middle Eastern (MID)
AF:
0.100
AC:
10
AN:
100
European-Non Finnish (NFE)
AF:
0.0581
AC:
2733
AN:
47030
Other (OTH)
AF:
0.0988
AC:
115
AN:
1164
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
292
584
876
1168
1460
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
104
208
312
416
520
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
-2.4
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs369756092; hg19: chr16-46694101; API