3-184879292-A-T

Variant names:

• chr3-184879292-A-T
• rs11717139
• NM_001009921.3:c.1735-6818A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001009921.3(VPS8):​c.1735-6818A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VPS8 NM_001009921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.467
• Publications: 3 publications found

Genes affected

VPS8 (HGNC:29122): (VPS8 subunit of CORVET complex) Predicted to enable metal ion binding activity. Involved in endosomal vesicle fusion. Located in early endosome. [provided by Alliance of Genome Resources, Apr 2022]

VPS8 Gene-Disease associations (from GenCC):

• arthrogryposis multiplex congenita

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

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=-0.6).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009921.3. 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
	VPS8	NM_001009921.3	MANE Select	c.1735-6818A>T		intron	N/A	NP_001009921.1	Q8N3P4-1
	VPS8	NM_001349292.2		c.1735-6818A>T		intron	N/A	NP_001336221.1	Q8N3P4-1
	VPS8	NM_001349293.2		c.1735-6818A>T		intron	N/A	NP_001336222.1	Q8N3P4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS8	ENST00000625842.3	TSL:5 MANE Select	c.1735-6818A>T		intron	N/A	ENSP00000487164.1	Q8N3P4-1
	VPS8	ENST00000287546.8	TSL:1	c.1735-6818A>T		intron	N/A	ENSP00000287546.4	C9JJN9
	VPS8	ENST00000446204.6	TSL:1	c.1728+8487A>T		intron	N/A	ENSP00000405483.2	Q8N3P4-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		0.47

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: rs11717139; hg19: chr3-184597080;