Variant 7-55572285-C-G 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.40G>C(p.Gly14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 1,368,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VOPP1
NM_030796.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.319

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=0.095223665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VOPP1	NM_030796.5 linkuse as main transcript	c.40G>C	p.Gly14Arg	missense_variant	1/5	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.40G>C	p.Gly14Arg	missense_variant	1/5	1	NM_030796.5	ENSP00000285279	P1	Q96AW1-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151878

Hom.:

Cov.:

FAILED QC

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:

0.0000950

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000658

AC:

AN:

1368718

Hom.:

Cov.:

AF XY:

0.0000103

AC XY:

AN XY:

677652

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000258

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000465

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000658

AC:

AN:

151878

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74184

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:

0.0000950

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000184

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

Nov 08, 2022

The c.40G>C (p.G14R) alteration is located in exon 1 (coding exon 1) of the VOPP1 gene. This alteration results from a G to C substitution at nucleotide position 40, causing the glycine (G) at amino acid position 14 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

Pathogenic

0.61

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.011

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.57

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.095

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.68

REVEL

Benign

0.041

Sift

Benign

0.045

Sift4G

Benign

0.57

Polyphen

0.0

Vest4

0.25

MutPred

0.57

Gain of MoRF binding (P = 0.0068);

MVP

0.16

MPC

0.25

ClinPred

0.080

GERP RS

0.93

Varity_R

0.069

gMVP

0.84

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