Variant 17-59839807-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_030938.5(VMP1):c.1117G>A(p.Val373Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000037 in 1,460,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

VMP1
NM_030938.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.917

Variant links:

Genes affected

VMP1 (HGNC:29559): (vacuole membrane protein 1) This gene encodes a transmembrane protein that plays a key regulatory role in the process of autophagy. The ectopic overexpression of the encoded protein in cultured cells triggers autophagy even under nutrient-rich conditions. This gene is overexpressed in pancreatitis affected acinar cells where the encoded protein mediates sequestration and degradation of potentially deleterious activated zymogen granules in a process termed, zymophagy. [provided by RefSeq, Jul 2016]

VMP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036989838).

BS2

High AC in GnomAdExome4 at 54 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VMP1	NM_030938.5 linkuse as main transcript	c.1117G>A	p.Val373Ile	missense_variant	12/12	ENST00000262291.9	NP_112200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VMP1	ENST00000262291.9 linkuse as main transcript	c.1117G>A	p.Val373Ile	missense_variant	12/12	1	NM_030938.5	ENSP00000262291	P1	Q96GC9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250044

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135200

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1460616

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726618

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Dec 15, 2021

The c.1117G>A (p.V373I) alteration is located in exon 12 (coding exon 11) of the VMP1 gene. This alteration results from a G to A substitution at nucleotide position 1117, causing the valine (V) at amino acid position 373 to be replaced by an isoleucine (I). 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

0.063

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.035

T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.0024

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.57

N;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.38

N;.

REVEL

Benign

0.032

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.058

MutPred

0.44

Loss of catalytic residue at V373 (P = 0.0486);.;

MVP

0.043

MPC

0.54

ClinPred

0.057

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.028

gMVP

0.19

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