NM_007259.5:c.27G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_007259.5(VPS45):​c.27G>C​(p.Gln9His) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q9Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

VPS45
NM_007259.5 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.30

Publications

0 publications found
Variant links:
Genes affected
VPS45 (HGNC:14579): (vacuolar protein sorting 45 homolog) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene is a member of the Sec1 domain family, and shows a high degree of sequence similarity to mouse, rat and yeast Vps45. The exact function of this gene is not known, but its high expression in peripheral blood mononuclear cells suggests a role in trafficking proteins, including inflammatory mediators. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2013]
OTUD7B (HGNC:16683): (OTU deubiquitinase 7B) Enables Lys48-specific deubiquitinase activity and thiol-dependent deubiquitinase. Involved in several processes, including negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of macromolecule metabolic process; and protein deubiquitination. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3270958).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VPS45NM_007259.5 linkc.27G>C p.Gln9His missense_variant Exon 1 of 15 ENST00000644510.2 NP_009190.2 Q9NRW7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VPS45ENST00000644510.2 linkc.27G>C p.Gln9His missense_variant Exon 1 of 15 NM_007259.5 ENSP00000495563.1 Q9NRW7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461856
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727222
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000809
AC:
9
AN:
1111990
Other (OTH)
AF:
0.00
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.453
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
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
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Benign
19
DANN
Benign
0.94
DEOGEN2
Benign
0.083
T;.;T;.;.;.
Eigen
Benign
-0.035
Eigen_PC
Benign
0.12
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.40
.;T;D;D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.33
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M;.;M;.;.;.
PhyloP100
5.3
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-1.4
N;.;.;.;N;.
REVEL
Benign
0.16
Sift
Benign
0.55
T;.;.;.;T;.
Sift4G
Benign
0.21
T;D;.;.;T;.
Polyphen
0.14
B;.;B;.;.;.
Vest4
0.65
MutPred
0.43
Loss of MoRF binding (P = 0.0845);Loss of MoRF binding (P = 0.0845);Loss of MoRF binding (P = 0.0845);Loss of MoRF binding (P = 0.0845);Loss of MoRF binding (P = 0.0845);Loss of MoRF binding (P = 0.0845);
MVP
0.48
MPC
0.32
ClinPred
0.62
D
GERP RS
4.1
PromoterAI
-0.054
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.38
gMVP
0.59
Mutation Taster
=56/44
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: rs1654813865; hg19: chr1-150039941; API