Variant 3-184834639-T-C details in Genebe, Genetics Data Aggregator

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

Splicing: ADA: 0.0005549

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]

VPS8 links:

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	Protein	UniProt
VPS8	NM_001009921.3 linkuse as main transcript	c.354-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000625842.3	NP_001009921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS8	ENST00000625842.3 linkuse as main transcript	c.354-10T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001009921.3	ENSP00000487164	A1	Q8N3P4-1

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152196

Hom.:

Cov.:

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:

AN:

139300

Hom.:

AF XY:

0.000586

AC XY:

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.:

Cov.:

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:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

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.:

Bravo

AF:

0.000461

Asia WGS

AF:

0.000868

AC:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over