GeneBe

rs921803718

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013265.4(VPS51):​c.64C>G​(p.Pro22Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P22S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

VPS51
NM_013265.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0250

Publications

0 publications found
Variant links:
Genes affected
VPS51 (HGNC:1172): (VPS51 subunit of GARP complex) This gene encodes a member of the vacuolar protein sorting-associated protein 51 family. The encoded protein is a component of the Golgi-associated retrograde protein complex which acts as a tethering factor for carriers in retrograde transport from the early and late endosomes to the trans-Golgi network. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]
VPS51 Gene-Disease associations (from GenCC):
  • pontocerebellar hypoplasia, type 13
    Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09801331).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013265.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
VPS51
NM_013265.4
MANE Select
c.64C>Gp.Pro22Ala
missense
Exon 1 of 10NP_037397.2
VPS51
NR_073519.2
n.101C>G
non_coding_transcript_exon
Exon 1 of 10

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
VPS51
ENST00000279281.8
TSL:1 MANE Select
c.64C>Gp.Pro22Ala
missense
Exon 1 of 10ENSP00000279281.3Q9UID3-1
VPS51
ENST00000940630.1
c.64C>Gp.Pro22Ala
missense
Exon 1 of 7ENSP00000610689.1
VPS51
ENST00000529180.1
TSL:3
c.64C>Gp.Pro22Ala
missense
Exon 1 of 4ENSP00000435245.1E9PKX7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.055
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
17
DANN
Benign
0.96
DEOGEN2
Benign
0.0096
T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.085
N
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.098
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.83
L
PhyloP100
0.025
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.14
N
REVEL
Benign
0.027
Sift
Benign
0.083
T
Sift4G
Benign
0.33
T
Polyphen
0.028
B
Vest4
0.18
MutPred
0.11
Gain of helix (P = 0.0349)
MVP
0.099
MPC
0.67
ClinPred
0.16
T
GERP RS
3.4
PromoterAI
0.030
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.051
gMVP
0.15
Mutation Taster
=93/7
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: rs921803718; hg19: chr11-64863786; API