rs150076399

Variant names:

• chr1-150076261-C-T
• rs150076399
• NM_007259.5:c.318C>T
• VPS45 p.Asp106Asp

Your query was ambiguous. Multiple possible variants found:

• chr1-150076261-C-T
• chr1-150076261-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.594
• Publications: 1 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007259.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS45	NM_007259.5	MANE Select	c.318C>T	p.Asp106Asp	synonymous	Exon 4 of 15	NP_009190.2
	VPS45	NM_001279353.2		c.210C>T	p.Asp70Asp	synonymous	Exon 4 of 14	NP_001266282.1	Q9NRW7-2
	VPS45	NM_001279354.2		c.210C>T	p.Asp70Asp	synonymous	Exon 4 of 15	NP_001266283.1	A0A2R8YE10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS45	ENST00000644510.2	MANE Select	c.318C>T	p.Asp106Asp	synonymous	Exon 4 of 15	ENSP00000495563.1	Q9NRW7-1
	VPS45	ENST00000698584.1		c.318C>T	p.Asp106Asp	synonymous	Exon 4 of 16	ENSP00000513813.1	A0A8V8TM00
	VPS45	ENST00000644526.2		c.318C>T	p.Asp106Asp	synonymous	Exon 4 of 16	ENSP00000494363.1	A0A2R8YD95

Frequencies

GnomAD3 genomes AF: 0.000910 AC: 137 AN: 150572 Hom.: 0 Cov.: 30

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: 82 AN: 249636 AF XY: 0.000267

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.: 0 Cov.: 30 AF XY: 0.0000993 AC XY: 72 AN XY: 725018

African (AFR) AF: 0.00310 AC: 103 AN: 33230

American (AMR) AF: 0.0000675 AC: 3 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39442

South Asian (SAS) AF: 0.000268 AC: 23 AN: 85846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5746

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1109048

Other (OTH) AF: 0.000150 AC: 9 AN: 60082

GnomAD4 genome AF: 0.000903 AC: 136 AN: 150690 Hom.: 0 Cov.: 30 AF XY: 0.00112 AC XY: 82 AN XY: 73504

African (AFR) AF: 0.00305 AC: 125 AN: 40952

American (AMR) AF: 0.000401 AC: 6 AN: 14974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000633 AC: 3 AN: 4738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67852

Other (OTH) AF: 0.000964 AC: 2 AN: 2074

Alfa AF: 0.000704 Hom.: 0

Bravo AF: 0.000880

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000597

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Congenital neutropenia-myelofibrosis-nephromegaly syndrome (2)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	VPS45-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.3
DANN	Benign	0.47
PhyloP100		-0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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

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

Other links and lift over

dbSNP: rs150076399;

hg19: chr1-150048339;