6-142198478-C-G

Variant summary

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

The NM_016485.5(VTA1):ā€‹c.560C>Gā€‹(p.Pro187Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,948 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

VTA1
NM_016485.5 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.18
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]

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=0.085009396).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VTA1NM_016485.5 linkuse as main transcriptc.560C>G p.Pro187Arg missense_variant 6/8 ENST00000367630.9 NP_057569.2
VTA1NM_001286371.2 linkuse as main transcriptc.560C>G p.Pro187Arg missense_variant 6/7 NP_001273300.1
VTA1NM_001286372.2 linkuse as main transcriptc.386C>G p.Pro129Arg missense_variant 5/6 NP_001273301.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VTA1ENST00000367630.9 linkuse as main transcriptc.560C>G p.Pro187Arg missense_variant 6/81 NM_016485.5 ENSP00000356602 P1Q9NP79-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152104
Hom.:
0
Cov.:
32
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:
0.000578
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251300
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135822
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000327
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461726
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
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
AF:
0.0000197
AC:
3
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000412
AC:
5

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 submitterclinical testingAmbry GeneticsMay 30, 2023The c.560C>G (p.P187R) alteration is located in exon 6 (coding exon 6) of the VTA1 gene. This alteration results from a C to G substitution at nucleotide position 560, causing the proline (P) at amino acid position 187 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
0.12
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.091
.;T;T;.
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.83
T;T;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.085
T;T;T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Uncertain
2.1
.;.;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-3.3
D;.;D;N
REVEL
Benign
0.088
Sift
Benign
0.11
T;.;T;D
Sift4G
Benign
0.13
T;T;T;T
Polyphen
0.71
.;.;P;.
Vest4
0.26
MutPred
0.46
.;Gain of catalytic residue at P187 (P = 0.0127);Gain of catalytic residue at P187 (P = 0.0127);.;
MVP
0.72
MPC
0.097
ClinPred
0.33
T
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.12
gMVP
0.36

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.

Other links and lift over

dbSNP: rs534195199; hg19: chr6-142519615; API