Variant 6-142218627-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016485.5(VTA1):c.908C>T(p.Thr303Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000892 in 1,457,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

VTA1
NM_016485.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

Variant links:

Genes affected

VTA1 (HGNC:20954): (vesicle trafficking 1) C6ORF55 encodes a protein involved in trafficking of the multivesicular body, an endosomal compartment involved in sorting membrane proteins for degradation in lysosomes (Ward et al., 2005 [PubMed 15644320]).[supplied by OMIM, Mar 2008]

VTA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40011486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VTA1	NM_016485.5 linkuse as main transcript	c.908C>T	p.Thr303Met	missense_variant	8/8	ENST00000367630.9	NP_057569.2	Q9NP79-1
VTA1	NM_001286371.2 linkuse as main transcript	c.827C>T	p.Thr276Met	missense_variant	7/7		NP_001273300.1	Q9NP79A0A087WY55
VTA1	NM_001286372.2 linkuse as main transcript	c.653C>T	p.Thr218Met	missense_variant	6/6		NP_001273301.1	Q9NP79-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VTA1	ENST00000367630.9 linkuse as main transcript	c.908C>T	p.Thr303Met	missense_variant	8/8	1	NM_016485.5	ENSP00000356602.3	Q9NP79-1
VTA1	ENST00000620996.4 linkuse as main transcript	c.827C>T	p.Thr276Met	missense_variant	7/7	3		ENSP00000481525.1	A0A087WY55
VTA1	ENST00000367621.1 linkuse as main transcript	c.734C>T	p.Thr245Met	missense_variant	7/7	5		ENSP00000356593.1	Q5TGM0
VTA1	ENST00000452973.6 linkuse as main transcript	c.653C>T	p.Thr218Met	missense_variant	6/6	2		ENSP00000395767.2	Q9NP79-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000811

AC:

AN:

246544

Hom.:

AF XY:

0.00000751

AC XY:

AN XY:

133174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000341

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000892

AC:

AN:

1457778

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

724920

show subpopulations

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:

0.0000470

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

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

May 27, 2022

The c.908C>T (p.T303M) alteration is located in exon 8 (coding exon 8) of the VTA1 gene. This alteration results from a C to T substitution at nucleotide position 908, causing the threonine (T) at amino acid position 303 to be replaced by a methionine (M). 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

0.14

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

.;T;T;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.40

T;T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.0

.;.;M;.

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.6

D;.;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0040

D;.;D;D

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

1.0

.;.;D;.

Vest4

0.19

MutPred

0.58

.;.;Loss of relative solvent accessibility (P = 0.0414);.;

MVP

0.67

MPC

0.11

ClinPred

0.80

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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