Genetic Variant VOPP1:p.Gly126Arg (chr7-55472998-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_030796.5(VOPP1):c.376G>A(p.Gly126Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000047 in 1,596,700 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 0.00023 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

VOPP1
NM_030796.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75

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:

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=0.085690945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VOPP1	NM_030796.5 link	c.376G>A	p.Gly126Arg	missense_variant	Exon 5 of 5	ENST00000285279.10	NP_110423.3	Q96AW1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VOPP1	ENST00000285279.10 link	c.376G>A	p.Gly126Arg	missense_variant	Exon 5 of 5	1	NM_030796.5	ENSP00000285279.5		Q96AW1-1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000480

GnomAD3 exomes

AF:

0.0000603

AC:

AN:

232190

Hom.:

AF XY:

0.0000474

AC XY:

AN XY:

126700

show subpopulations

Gnomad AFR exome

AF:

0.000685

Gnomad AMR exome

AF:

0.000135

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.0000277

AC:

AN:

1444694

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

718422

show subpopulations

Gnomad4 AFR exome

AF:

0.000767

Gnomad4 AMR exome

AF:

0.0000979

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:

0.00

Gnomad4 OTH exome

AF:

0.000184

GnomAD4 genome

AF:

0.000230

AC:

AN:

152006

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.000797

Gnomad4 AMR

AF:

0.0000655

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:

0.000480

Alfa

AF:

0.000197

Hom.:

Bravo

AF:

0.000348

ESP6500AA

AF:

0.000805

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000662

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.376G>A (p.G126R) 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 376, causing the glycine (G) at amino acid position 126 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

0.27

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

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

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.29

LIST_S2

Uncertain

0.96

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

M_CAP

Benign

0.0045

MetaRNN

Benign

0.086

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

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.90

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

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.5

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

REVEL

Benign

0.13

Sift

Benign

0.086

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

Sift4G

Benign

0.35

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

Polyphen

0.99

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

Vest4

0.39

MutPred

0.33

Gain of methylation at G126 (P = 0.0176);.;.;.;.;.;.;.;.;.;.;

MVP

0.18

MPC

0.81

ClinPred

0.096

GERP RS

5.6

Varity_R

0.12

gMVP

0.62

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