Variant 11-65096393-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000279281.8(VPS51):c.143C>T(p.Ala48Val) variant causes a missense 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VPS51
ENST00000279281.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.299

Variant links:

Genes affected

VPS51 (HGNC:1172): (VPS51 subunit of GARP complex) This gene encodes a member of the vacuolar protein sorting-associated protein 51 family. The encoded protein is a component of the Golgi-associated retrograde protein complex which acts as a tethering factor for carriers in retrograde transport from the early and late endosomes to the trans-Golgi network. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

VPS51 links:

VPS51 (HGNC:):

VPS51 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06858057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS51	NM_013265.4 linkuse as main transcript	c.143C>T	p.Ala48Val	missense_variant	1/10	ENST00000279281.8	NP_037397.2	Q9UID3-1
VPS51	NR_073519.2 linkuse as main transcript	n.180C>T		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS51	ENST00000279281.8 linkuse as main transcript	c.143C>T	p.Ala48Val	missense_variant	1/10	1	NM_013265.4	ENSP00000279281.3		Q9UID3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1374418

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680124

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.143C>T (p.A48V) alteration is located in exon 1 (coding exon 1) of the VPS51 gene. This alteration results from a C to T substitution at nucleotide position 143, causing the alanine (A) at amino acid position 48 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;T;T;T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.71

T;T;T;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.069

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;.;L;.;.

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.5

N;N;N;N;.

REVEL

Benign

0.033

Sift

Benign

0.17

T;T;T;T;.

Sift4G

Uncertain

0.049

D;T;T;T;.

Polyphen

0.27

.;.;B;.;.

Vest4

0.074

MutPred

0.23

.;Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);

MVP

0.081

MPC

0.89

ClinPred

0.39

GERP RS

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.048

gMVP

0.20

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

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