GeneBe

rs369756092

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_018206.6(VPS35):​c.*282_*283insAA 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 0.085 ( 713 hom., cov: 0)
Exomes 𝑓: 0.084 ( 295 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: Benign. The variant received -8 ACMG points.

BA1
GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

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.*282_*283insAA
3_prime_UTR
Exon 17 of 17NP_060676.2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
VPS35
ENST00000299138.12
TSL:1 MANE Select
c.*282_*283insAA
3_prime_UTR
Exon 17 of 17ENSP00000299138.7Q96QK1
VPS35
ENST00000568784.6
TSL:1
n.*3343_*3344insAA
non_coding_transcript_exon
Exon 17 of 17ENSP00000456274.2H3BRJ7
VPS35
ENST00000568784.6
TSL:1
n.*3343_*3344insAA
3_prime_UTR
Exon 17 of 17ENSP00000456274.2H3BRJ7

Frequencies

GnomAD3 genomes
AF:
0.0849
AC:
7617
AN:
89758
Hom.:
710
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0463
Gnomad AMI
AF:
0.135
Gnomad AMR
AF:
0.0734
Gnomad ASJ
AF:
0.0622
Gnomad EAS
AF:
0.0106
Gnomad SAS
AF:
0.0186
Gnomad FIN
AF:
0.0856
Gnomad MID
AF:
0.0943
Gnomad NFE
AF:
0.114
Gnomad OTH
AF:
0.0947
GnomAD4 exome
AF:
0.0842
AC:
720
AN:
8548
Hom.:
295
Cov.:
0
AF XY:
0.0855
AC XY:
375
AN XY:
4384
show subpopulations
African (AFR)
AF:
0.0339
AC:
8
AN:
236
American (AMR)
AF:
0.0952
AC:
64
AN:
672
Ashkenazi Jewish (ASJ)
AF:
0.0613
AC:
13
AN:
212
East Asian (EAS)
AF:
0.0472
AC:
17
AN:
360
South Asian (SAS)
AF:
0.0589
AC:
78
AN:
1324
European-Finnish (FIN)
AF:
0.0743
AC:
26
AN:
350
Middle Eastern (MID)
AF:
0.219
AC:
7
AN:
32
European-Non Finnish (NFE)
AF:
0.0943
AC:
461
AN:
4890
Other (OTH)
AF:
0.0975
AC:
46
AN:
472
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.479
Heterozygous variant carriers
0
6
11
17
22
28
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4
8
12
16
20
<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:
0.0849
AC:
7619
AN:
89772
Hom.:
713
Cov.:
0
AF XY:
0.0809
AC XY:
3240
AN XY:
40026
show subpopulations
African (AFR)
AF:
0.0465
AC:
1201
AN:
25852
American (AMR)
AF:
0.0737
AC:
480
AN:
6514
Ashkenazi Jewish (ASJ)
AF:
0.0622
AC:
159
AN:
2556
East Asian (EAS)
AF:
0.0101
AC:
23
AN:
2268
South Asian (SAS)
AF:
0.0182
AC:
39
AN:
2146
European-Finnish (FIN)
AF:
0.0856
AC:
121
AN:
1414
Middle Eastern (MID)
AF:
0.0600
AC:
6
AN:
100
European-Non Finnish (NFE)
AF:
0.114
AC:
5397
AN:
47154
Other (OTH)
AF:
0.0961
AC:
112
AN:
1166
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
233
466
698
931
1164
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
76
152
228
304
380
<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

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

Other links and lift over

dbSNP: rs369756092; hg19: chr16-46694097; COSMIC: COSV54476783; COSMIC: COSV54476783; API
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