rs1480253653

Variant names:

• chr11-119067876-T-G
• rs1480253653
• NM_021729.6:c.53T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021729.6(VPS11):​c.53T>G​(p.Val18Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V18M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: VPS11 NM_021729.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• Publications: 0 publications found

Genes affected

VPS11 (HGNC:14583): (VPS11 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 Vps11 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

VPS11-DT (HGNC:55227): (VPS11 divergent transcript)

LOC124902769 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021729.6. 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
	VPS11	NM_021729.6	MANE Select	c.53T>G	p.Val18Gly	missense	Exon 1 of 16	NP_068375.3
	VPS11	NM_001378218.1		c.53T>G	p.Val18Gly	missense	Exon 1 of 16	NP_001365147.1
	VPS11	NM_001378219.1		c.53T>G	p.Val18Gly	missense	Exon 1 of 16	NP_001365148.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS11	ENST00000621676.5	TSL:1 MANE Select	c.53T>G	p.Val18Gly	missense	Exon 1 of 16	ENSP00000481126.1	A0A087WXL6
	VPS11	ENST00000952525.1		c.53T>G	p.Val18Gly	missense	Exon 1 of 16	ENSP00000622584.1
	VPS11	ENST00000863302.1		c.53T>G	p.Val18Gly	missense	Exon 1 of 16	ENSP00000533361.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	27
DANN	Benign	0.87
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Uncertain	0.72	D
PhyloP100		4.0
PrimateAI	Uncertain	0.62	T
Sift4G	Benign	0.10	T
Vest4		0.59
MVP		0.58
GERP RS		4.0
PromoterAI		-0.035	Neutral
gMVP		0.89
Mutation Taster		=59/41	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

Other links and lift over

dbSNP: rs1480253653; hg19: chr11-118938587;