11-119067875-G-A

Variant names:

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

Variant summary

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

The NM_001290185.2(VPS11):​c.-194G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,577,222 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• 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 0 ACMG points.

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>A	p.Val18Met	missense	Exon 1 of 16	NP_068375.3
	VPS11	NM_001290185.2		c.-194G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	NP_001277114.1	B7Z879
	VPS11	NM_001378218.1		c.52G>A	p.Val18Met	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>A	p.Val18Met	missense	Exon 1 of 16	ENSP00000481126.1	A0A087WXL6
	VPS11	ENST00000614944.4	TSL:2	c.-194G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000481807.1	B7Z879
	VPS11	ENST00000952525.1		c.52G>A	p.Val18Met	missense	Exon 1 of 16	ENSP00000622584.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152254 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000491 AC: 7 AN: 1424968 Hom.: 0 Cov.: 31 AF XY: 0.00000425 AC XY: 3 AN XY: 705658

African (AFR) AF: 0.00 AC: 0 AN: 32668

American (AMR) AF: 0.000130 AC: 5 AN: 38458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25570

East Asian (EAS) AF: 0.00 AC: 0 AN: 37864

South Asian (SAS) AF: 0.00 AC: 0 AN: 81790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093222

Other (OTH) AF: 0.0000339 AC: 2 AN: 58994

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152254 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74386

African (AFR) AF: 0.00 AC: 0 AN: 41478

American (AMR) AF: 0.00105 AC: 16 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000302

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	Benign	0.32
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Benign	0.95
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.48	T
PhyloP100		7.8
PrimateAI	Uncertain	0.72	T
Sift4G	Uncertain	0.018	D
Vest4		0.56
MVP		0.49
GERP RS		5.2
PromoterAI		0.0049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
gMVP		0.64
Mutation Taster		=53/47	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;