1-150076261-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_007259.5(VPS45):c.318C>T(p.Asp106Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,607,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00090 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

VPS45
NM_007259.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.594

Publications

1 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]

VPS45 Gene-Disease associations (from GenCC):

congenital neutropenia-myelofibrosis-nephromegaly syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

VPS45 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-150076261-C-T is Benign according to our data. Variant chr1-150076261-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 437261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.594 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS45	NM_007259.5 link	c.318C>T	p.Asp106Asp	synonymous_variant	Exon 4 of 15	ENST00000644510.2	NP_009190.2	Q9NRW7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS45	ENST00000644510.2 link	c.318C>T	p.Asp106Asp	synonymous_variant	Exon 4 of 15		NM_007259.5	ENSP00000495563.1		Q9NRW7-1

Frequencies

GnomAD3 genomes

AF:

0.000910

AC:

137

AN:

150572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000401

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000633

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000975

GnomAD2 exomes

AF:

0.000328

AC:

AN:

249636

AF XY:

0.000267

show subpopulations

Gnomad AFR exome

AF:

0.00425

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000995

AC:

145

AN:

1457118

Hom.:

Cov.:

AF XY:

0.0000993

AC XY:

AN XY:

725018

show subpopulations

African (AFR)

AF:

0.00310

AC:

103

AN:

33230

American (AMR)

AF:

0.0000675

AC:

AN:

44476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26016

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39442

South Asian (SAS)

AF:

0.000268

AC:

AN:

85846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53232

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1109048

Other (OTH)

AF:

0.000150

AC:

AN:

60082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

AF:

0.000903

AC:

136

AN:

150690

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

73504

show subpopulations

African (AFR)

AF:

0.00305

AC:

125

AN:

40952

American (AMR)

AF:

0.000401

AC:

AN:

14974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.000633

AC:

AN:

4738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67852

Other (OTH)

AF:

0.000964

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000704

Hom.:

Bravo

AF:

0.000880

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000597

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital neutropenia-myelofibrosis-nephromegaly syndrome

Benign:2

Dec 18, 2019

Natera, Inc.

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 19, 2016

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

VPS45-related disorder

Benign:1

Nov 26, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

VPS45: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.3

(source)

DANN

Benign

0.47

PhyloP100

-0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over