chr11-119067836-C-T

Variant names:

• chr11-119067836-C-T
• rs979238008
• NM_021729.6:c.13C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001290185.2(VPS11):​c.-233C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,549,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: VPS11 NM_001290185.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 11-119067836-C-T is Benign according to our data. Variant chr11-119067836-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2065202.Status of the report is criteria_provided_single_submitter, 1 stars.

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.13C>T	p.Leu5Leu	synonymous	Exon 1 of 16	NP_068375.3
	VPS11	NM_001290185.2		c.-233C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	NP_001277114.1	B7Z879
	VPS11	NM_001378218.1		c.13C>T	p.Leu5Leu	synonymous	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.13C>T	p.Leu5Leu	synonymous	Exon 1 of 16	ENSP00000481126.1	A0A087WXL6
	VPS11	ENST00000614944.4	TSL:2	c.-233C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000481807.1	B7Z879
	VPS11	ENST00000952525.1		c.13C>T	p.Leu5Leu	synonymous	Exon 1 of 16	ENSP00000622584.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD2 exomes AF: 0.0000124 AC: 2 AN: 160696 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000803

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1397238 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 688538

African (AFR) AF: 0.00 AC: 0 AN: 31706

American (AMR) AF: 0.0000558 AC: 2 AN: 35870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25232

East Asian (EAS) AF: 0.00 AC: 0 AN: 35990

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5100

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077064

Other (OTH) AF: 0.00 AC: 0 AN: 57786

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	13
DANN	Benign	0.95
PhyloP100		1.3
PromoterAI		0.13	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs979238008; hg19: chr11-118938547;