Variant chr7-55472919-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_030796.5(VOPP1):c.455C>T(p.Pro152Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000213 in 1,542,406 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

VOPP1
NM_030796.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

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:

VOPP1 (HGNC:):

VOPP1 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=0.36363178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VOPP1	NM_030796.5 linkuse as main transcript	c.455C>T	p.Pro152Leu	missense_variant	5/5	ENST00000285279.10	NP_110423.3	Q96AW1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VOPP1	ENST00000285279.10 linkuse as main transcript	c.455C>T	p.Pro152Leu	missense_variant	5/5	1	NM_030796.5	ENSP00000285279.5		Q96AW1-1

Frequencies

GnomAD3 genomes

AF:

0.000147

AC:

AN:

149866

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000466

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000198

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000208

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000756

AC:

AN:

171992

Hom.:

AF XY:

0.0000726

AC XY:

AN XY:

96454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000450

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000110

Gnomad OTH exome

AF:

0.000262

GnomAD4 exome

AF:

0.000220

AC:

307

AN:

1392426

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

145

AN XY:

690706

show subpopulations

Gnomad4 AFR exome

AF:

0.0000336

Gnomad4 AMR exome

AF:

0.000170

Gnomad4 ASJ exome

AF:

0.0000417

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000262

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000263

Gnomad4 OTH exome

AF:

0.000209

GnomAD4 genome

AF:

0.000147

AC:

AN:

149980

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

73172

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000466

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000198

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000208

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000192

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.0000499

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

Aug 17, 2021

The c.455C>T (p.P152L) alteration is located in exon 5 (coding exon 5) of the VOPP1 gene. This alteration results from a C to T substitution at nucleotide position 455, causing the proline (P) at amino acid position 152 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

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

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

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

M_CAP

Benign

0.016

MetaRNN

Benign

0.31

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

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.0

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.7

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

REVEL

Benign

0.27

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.012

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

Polyphen

1.0

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

Vest4

0.52

MutPred

0.35

Loss of glycosylation at P152 (P = 0.0238);.;.;.;.;.;.;.;.;.;.;

MVP

0.21

MPC

0.80

ClinPred

0.51

GERP RS

5.5

Varity_R

0.26

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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