chr1-150067930-C-T

Variant names:

• chr1-150067930-C-T
• rs782367453
• NM_007259.5:c.73C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_007259.5(VPS45):​c.73C>T​(p.Leu25Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. L25I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VPS45 NM_007259.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.62

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]

ENSG00000285184 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS45	NM_007259.5	c.73C>T	p.Leu25Phe	missense_variant	Exon 1 of 15	ENST00000644510.2	NP_009190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS45	ENST00000644510.2	c.73C>T	p.Leu25Phe	missense_variant	Exon 1 of 15		NM_007259.5	ENSP00000495563.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	D;D;.;.;.
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Benign	0.43	N
LIST_S2	Pathogenic	0.99	.;D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.90	D;D;D;D;D
MetaSVM	Pathogenic	0.99	D
MutationAssessor	Pathogenic	3.4	M;M;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.4	D;.;.;D;.
REVEL	Pathogenic	0.87
Sift	Uncertain	0.0020	D;.;.;T;.
Sift4G	Uncertain	0.024	D;.;.;D;.
Polyphen		1.0	D;D;.;.;.
Vest4		0.86
MutPred		0.70		Gain of methylation at K23 (P = 0.0807);Gain of methylation at K23 (P = 0.0807);Gain of methylation at K23 (P = 0.0807);Gain of methylation at K23 (P = 0.0807);Gain of methylation at K23 (P = 0.0807);
MVP		0.90
MPC		1.0
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.85
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs782367453; hg19: chr1-150039987;