Variant 7-55472983-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 NM_030796.5(VOPP1):c.391G>A(p.Gly131Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000565 in 1,592,412 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: 20)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

VOPP1
NM_030796.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

Variant links:

Genes affected

VOPP1 (HGNC:34518): (VOPP1 WW domain binding protein) Located in cytoplasmic vesicle membrane and endosome. Is integral component of organelle membrane. [provided by Alliance of Genome Resources, Apr 2022]

VOPP1 links:

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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=0.1591838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VOPP1	NM_030796.5 linkuse as main transcript	c.391G>A	p.Gly131Arg	missense_variant	5/5	ENST00000285279.10	NP_110423.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VOPP1	ENST00000285279.10 linkuse as main transcript	c.391G>A	p.Gly131Arg	missense_variant	5/5	1	NM_030796.5	ENSP00000285279	P1	Q96AW1-1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000555

AC:

AN:

1440566

Hom.:

Cov.:

AF XY:

0.00000558

AC XY:

AN XY:

716466

show subpopulations

Gnomad4 AFR exome

AF:

0.0000617

Gnomad4 AMR exome

AF:

0.0000254

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:

0.00000362

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000248

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

Jun 02, 2023

The c.391G>A (p.G131R) alteration is located in exon 5 (coding exon 5) of the VOPP1 gene. This alteration results from a G to A substitution at nucleotide position 391, causing the glycine (G) at amino acid position 131 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

0.26

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

T;.;.;.;.;.;.;.;.;.;.

Eigen

Benign

-0.044

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.37

LIST_S2

Uncertain

0.94

D;D;.;.;D;D;D;D;D;D;D

M_CAP

Benign

0.0096

MetaRNN

Benign

0.16

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.90

L;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.91

D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.1

N;N;D;D;.;N;D;D;N;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.0030

D;D;D;D;.;D;D;D;D;D;D

Sift4G

Uncertain

0.028

D;D;T;T;D;D;.;T;D;T;.

Polyphen

1.0

D;.;.;.;.;.;.;.;.;.;.

Vest4

0.55

MutPred

0.30

Gain of solvent accessibility (P = 0.0171);.;.;.;.;.;.;.;.;.;.;

MVP

0.21

MPC

0.26

ClinPred

0.48

GERP RS

3.3

Varity_R

0.10

gMVP

0.69

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