3-185000930-G-T

Variant names:

• chr3-185000930-G-T
• rs10937194
• NM_001009921.3:c.4002+1069G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001009921.3(VPS8):​c.4002+1069G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,070 control chromosomes in the GnomAD database, including 36,610 homozygotes. 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: 𝑓 0.67 (36610 hom., cov: 31)
• Consequence: VPS8 NM_001009921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 4 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: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS8	NM_001009921.3	MANE Select	c.4002+1069G>T		intron	N/A	NP_001009921.1
	VPS8	NM_001349292.2		c.4002+1069G>T		intron	N/A	NP_001336221.1
	VPS8	NM_001349293.2		c.4002+1069G>T		intron	N/A	NP_001336222.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS8	ENST00000625842.3	TSL:5 MANE Select	c.4002+1069G>T		intron	N/A	ENSP00000487164.1
	VPS8	ENST00000287546.8	TSL:1	c.4002+1069G>T		intron	N/A	ENSP00000287546.4
	VPS8	ENST00000446204.6	TSL:1	c.3726+1069G>T		intron	N/A	ENSP00000405483.2

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101432 AN: 151952 Hom.: 36594 Cov.: 31

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.667 AC: 101486 AN: 152070 Hom.: 36610 Cov.: 31 AF XY: 0.673 AC XY: 50029 AN XY: 74374

African (AFR) AF: 0.368 AC: 15240 AN: 41436

American (AMR) AF: 0.786 AC: 12021 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2905 AN: 3470

East Asian (EAS) AF: 0.835 AC: 4310 AN: 5160

South Asian (SAS) AF: 0.713 AC: 3437 AN: 4822

European-Finnish (FIN) AF: 0.802 AC: 8493 AN: 10588

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52648 AN: 67996

Other (OTH) AF: 0.723 AC: 1523 AN: 2106

Alfa AF: 0.757 Hom.: 32463

Bravo AF: 0.656

Asia WGS AF: 0.758 AC: 2639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.53
PhyloP100		-0.065
Mutation Taster		=100/0	polymorphism (auto)

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: rs10937194; hg19: chr3-184718718;