Variant 6-142169560-A-G 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.218A>G(p.Gln73Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000747 in 1,607,028 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

VTA1
NM_016485.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.72

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=0.33812147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VTA1	NM_016485.5 linkuse as main transcript	c.218A>G	p.Gln73Arg	missense_variant	3/8	ENST00000367630.9	NP_057569.2
VTA1	NM_001286371.2 linkuse as main transcript	c.218A>G	p.Gln73Arg	missense_variant	3/7		NP_001273300.1
VTA1	NM_001286372.2 linkuse as main transcript	c.44A>G	p.Gln15Arg	missense_variant	2/6		NP_001273301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VTA1	ENST00000367630.9 linkuse as main transcript	c.218A>G	p.Gln73Arg	missense_variant	3/8	1	NM_016485.5	ENSP00000356602	P1	Q9NP79-1
VTA1	ENST00000620996.4 linkuse as main transcript	c.218A>G	p.Gln73Arg	missense_variant	3/7	3		ENSP00000481525
VTA1	ENST00000367621.1 linkuse as main transcript	c.44A>G	p.Gln15Arg	missense_variant	2/7	5		ENSP00000356593
VTA1	ENST00000452973.6 linkuse as main transcript	c.44A>G	p.Gln15Arg	missense_variant	2/6	2		ENSP00000395767		Q9NP79-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000756

AC:

AN:

1454766

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723468

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:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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 25, 2023

The c.218A>G (p.Q73R) alteration is located in exon 3 (coding exon 3) of the VTA1 gene. This alteration results from a A to G substitution at nucleotide position 218, causing the glutamine (Q) at amino acid position 73 to be replaced by an arginine (R). 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

0.20

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

.;T;T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;.;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.1

N;.;N;N

REVEL

Benign

0.20

Sift

Uncertain

0.029

D;.;D;D

Sift4G

Benign

0.20

T;T;T;T

Polyphen

0.74

.;.;P;.

Vest4

0.38

MutPred

0.36

.;Loss of ubiquitination at K71 (P = 0.0992);Loss of ubiquitination at K71 (P = 0.0992);.;

MVP

0.51

MPC

0.12

ClinPred

0.96

GERP RS

5.0

Varity_R

0.62

gMVP

0.29

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