Variant 7-55472878-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030796.5(VOPP1):c.496G>A(p.Glu166Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000071 in 1,407,912 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

VOPP1
NM_030796.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VOPP1	NM_030796.5 linkuse as main transcript	c.496G>A	p.Glu166Lys	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.496G>A	p.Glu166Lys	missense_variant	5/5	1	NM_030796.5	ENSP00000285279	P1	Q96AW1-1

Frequencies

GnomAD3 genomes

AF:

0.0000138

AC:

AN:

145146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000695

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:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000131

AC:

AN:

76244

Hom.:

AF XY:

0.0000234

AC XY:

AN XY:

42678

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000285

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000634

AC:

AN:

1262766

Hom.:

Cov.:

AF XY:

0.00000646

AC XY:

AN XY:

618884

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000665

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:

0.00000598

Gnomad4 OTH exome

AF:

0.0000190

GnomAD4 genome

AF:

0.0000138

AC:

AN:

145146

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

70338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000695

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000151

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000876

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

Sep 29, 2022

The c.496G>A (p.E166K) 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 496, causing the glutamic acid (E) at amino acid position 166 to be replaced by a lysine (K). 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

0.88

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.053

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

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

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

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.45

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

Pathogenic

0.80

PROVEAN

Uncertain

-2.4

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

REVEL

Benign

0.24

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.010

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

Polyphen

1.0

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

Vest4

0.80

MutPred

0.35

Gain of methylation at E166 (P = 0.0012);.;.;.;.;.;.;.;.;

MVP

0.37

MPC

0.83

ClinPred

0.68

GERP RS

5.5

Varity_R

0.34

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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