rs1307464180

Variant names:

• chr15-40894812-C-G
• rs1307464180
• NM_020857.3:c.44C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-40894812-C-G
• chr15-40894812-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020857.3(VPS18):​c.44C>G​(p.Ser15Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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. S15L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VPS18 NM_020857.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.41
• Publications: 0 publications found

Genes affected

VPS18 (HGNC:15972): (VPS18 core subunit of CORVET and HOPS complexes) 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 encodes the human homolog of yeast class C Vps18 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. [provided by RefSeq, Jul 2008]

VPS18 Gene-Disease associations (from GenCC):

• leukodystrophy

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

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=0.29408795).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020857.3. 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
	VPS18	NM_020857.3	MANE Select	c.44C>G	p.Ser15Trp	missense	Exon 1 of 5	NP_065908.1	Q9P253

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS18	ENST00000220509.10	TSL:1 MANE Select	c.44C>G	p.Ser15Trp	missense	Exon 1 of 5	ENSP00000220509.5	Q9P253
	VPS18	ENST00000943645.1		c.44C>G	p.Ser15Trp	missense	Exon 1 of 5	ENSP00000613704.1
	VPS18	ENST00000882105.1		c.44C>G	p.Ser15Trp	missense	Exon 1 of 5	ENSP00000552164.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.21
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.47
MutPred		0.31		Loss of disorder (P = 0.0012)
MVP		0.29
MPC		1.2
ClinPred		0.97	D
GERP RS		4.7
PromoterAI		0.0081	Neutral
Varity_R		0.30
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1307464180; hg19: chr15-41187010;