11-119067847-G-T

Variant names:

• chr11-119067847-G-T
• rs782083124
• NM_021729.6:c.24G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_021729.6(VPS11):​c.24G>T​(p.Arg8Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R8R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: VPS11 NM_021729.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=2.05 with no splicing effect.

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.24G>T	p.Arg8Arg	synonymous	Exon 1 of 16	NP_068375.3
	VPS11	NM_001378218.1		c.24G>T	p.Arg8Arg	synonymous	Exon 1 of 16	NP_001365147.1
	VPS11	NM_001378219.1		c.24G>T	p.Arg8Arg	synonymous	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.24G>T	p.Arg8Arg	synonymous	Exon 1 of 16	ENSP00000481126.1	A0A087WXL6
	VPS11	ENST00000952525.1		c.24G>T	p.Arg8Arg	synonymous	Exon 1 of 16	ENSP00000622584.1
	VPS11	ENST00000863302.1		c.24G>T	p.Arg8Arg	synonymous	Exon 1 of 16	ENSP00000533361.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000606 AC: 1 AN: 164882 AF XY: 0.0000114

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000152

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1401306 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 691010

African (AFR) AF: 0.00 AC: 0 AN: 31874

American (AMR) AF: 0.00 AC: 0 AN: 36130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25300

East Asian (EAS) AF: 0.00 AC: 0 AN: 36278

South Asian (SAS) AF: 0.00 AC: 0 AN: 79986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5216

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079368

Other (OTH) AF: 0.00 AC: 0 AN: 57982

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.92
PhyloP100		2.0
PromoterAI		0.070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs782083124; hg19: chr11-118938558;