11-119067875-G-C

Variant names:

• chr11-119067875-G-C
• rs868603899
• NM_021729.6:c.52G>C

Variant summary

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

The NM_001290185.2(VPS11):​c.-194G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: VPS11 NM_001290185.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.80
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28839874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290185.2. 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.52G>C	p.Val18Leu	missense	Exon 1 of 16	NP_068375.3
	VPS11	NM_001290185.2		c.-194G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	NP_001277114.1	B7Z879
	VPS11	NM_001378218.1		c.52G>C	p.Val18Leu	missense	Exon 1 of 16	NP_001365147.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS11	ENST00000621676.5	TSL:1 MANE Select	c.52G>C	p.Val18Leu	missense	Exon 1 of 16	ENSP00000481126.1	A0A087WXL6
	VPS11	ENST00000614944.4	TSL:2	c.-194G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000481807.1	B7Z879
	VPS11	ENST00000952525.1		c.52G>C	p.Val18Leu	missense	Exon 1 of 16	ENSP00000622584.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	23
DANN	Benign	0.90
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.29	T
PhyloP100		7.8
PrimateAI	Uncertain	0.69	T
Sift4G	Benign	0.20	T
Vest4		0.23
MVP		0.49
GERP RS		5.2
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
gMVP		0.59
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: rs868603899; hg19: chr11-118938586;