Variant 1-150076261-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007259.5(VPS45):c.318C>G(p.Asp106Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

VPS45
NM_007259.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.594

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]

VPS45 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1331104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS45	NM_007259.5 linkuse as main transcript	c.318C>G	p.Asp106Glu	missense_variant	4/15	ENST00000644510.2	NP_009190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS45	ENST00000644510.2 linkuse as main transcript	c.318C>G	p.Asp106Glu	missense_variant	4/15		NM_007259.5	ENSP00000495563	P3	Q9NRW7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249636

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135080

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457118

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725018

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.4

DANN

Benign

0.93

DEOGEN2

Benign

0.22

.;.;T;.;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.86

D;T;.;.;D;T;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.13

T;T;T;T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

2.0

.;.;M;.;M;.;.

MutationTaster

Benign

0.99

D;N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.1

.;.;N;N;.;N;.

REVEL

Uncertain

0.31

Sift

Benign

0.23

.;.;T;T;.;T;.

Sift4G

Benign

0.36

.;T;T;T;.;T;.

Polyphen

0.0030

.;.;B;.;B;.;.

Vest4

0.17, 0.17, 0.17

MutPred

0.51

.;.;Loss of ubiquitination at K104 (P = 0.0755);.;Loss of ubiquitination at K104 (P = 0.0755);Loss of ubiquitination at K104 (P = 0.0755);Loss of ubiquitination at K104 (P = 0.0755);

MVP

0.36

MPC

0.41

ClinPred

0.12

GERP RS

-6.1

Varity_R

0.10

gMVP

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over