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GeneBe

3-184834639-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001009921.3(VPS8):c.354-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000859 in 1,526,954 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00089 ( 1 hom. )

Consequence

VPS8
NM_001009921.3 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0005549
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0260
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 3-184834639-T-C is Benign according to our data. Variant chr3-184834639-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 732575.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VPS8NM_001009921.3 linkuse as main transcriptc.354-10T>C splice_polypyrimidine_tract_variant, intron_variant ENST00000625842.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VPS8ENST00000625842.3 linkuse as main transcriptc.354-10T>C splice_polypyrimidine_tract_variant, intron_variant 5 NM_001009921.3 A1Q8N3P4-1

Frequencies

GnomAD3 genomes
AF:
0.000572
AC:
87
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000999
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000625
AC:
87
AN:
139300
Hom.:
0
AF XY:
0.000586
AC XY:
43
AN XY:
73330
show subpopulations
Gnomad AFR exome
AF:
0.000128
Gnomad AMR exome
AF:
0.0000488
Gnomad ASJ exome
AF:
0.000256
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000604
Gnomad FIN exome
AF:
0.000137
Gnomad NFE exome
AF:
0.00119
Gnomad OTH exome
AF:
0.000519
GnomAD4 exome
AF:
0.000893
AC:
1227
AN:
1374640
Hom.:
1
Cov.:
30
AF XY:
0.000821
AC XY:
556
AN XY:
677438
show subpopulations
Gnomad4 AFR exome
AF:
0.000333
Gnomad4 AMR exome
AF:
0.0000637
Gnomad4 ASJ exome
AF:
0.000286
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00104
Gnomad4 FIN exome
AF:
0.0000221
Gnomad4 NFE exome
AF:
0.00101
Gnomad4 OTH exome
AF:
0.000825
GnomAD4 genome
AF:
0.000558
AC:
85
AN:
152314
Hom.:
0
Cov.:
32
AF XY:
0.000698
AC XY:
52
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00186
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000985
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00108
Hom.:
1
Bravo
AF:
0.000461
Asia WGS
AF:
0.000868
AC:
3
AN:
3472

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeNov 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
Cadd
Benign
1.1
Dann
Benign
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00055
dbscSNV1_RF
Benign
0.034
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs190794799; hg19: chr3-184552427; API