Variant X-151396898-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 ENST00000668689.1(ENSG00000287918):n.245C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000977 in 522,075 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 38 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.00012 ( 0 hom. 37 hem. )

Consequence

ENST00000668689.1 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -0.141

Variant links:

Genes affected

(HGNC:):

links:

VMA21 (HGNC:22082): (vacuolar ATPase assembly factor VMA21) This gene encodes a chaperone for assembly of lysosomal vacuolar ATPase.[provided by RefSeq, Jul 2012]

VMA21 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=0.021674305).

BS2

High Hemizygotes in GnomAdExome4 at 37 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VMA21	NM_001363810.1 linkuse as main transcript	c.59G>A	p.Cys20Tyr	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000668689.1 linkuse as main transcript	n.245C>T		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

AF:

0.0000181

AC:

AN:

110321

Hom.:

Cov.:

AF XY:

0.0000307

AC XY:

AN XY:

32563

show subpopulations

Gnomad AFR

AF:

0.0000330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000408

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000117

AC:

AN:

102579

Hom.:

AF XY:

0.000160

AC XY:

AN XY:

37389

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:

0.000861

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000119

AC:

AN:

411754

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

AN XY:

151836

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000181

AC:

AN:

110321

Hom.:

Cov.:

AF XY:

0.0000307

AC XY:

AN XY:

32563

show subpopulations

Gnomad4 AFR

AF:

0.0000330

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000408

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.000445

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

X-linked myopathy with excessive autophagy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Neuberg Centre For Genomic Medicine, NCGM

The missense c.59G>A(p.Cys20Tyr) variant in VMA21 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency 0.01% in the gnomAD and novel in 1000 genome. The amino acid Cys at position 20 is changed to a Tyr changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Uncertain Significance. -

VMA21-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 22, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.4

DANN

Benign

0.92

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.30

M_CAP

Benign

0.080

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.060

REVEL

Benign

0.010

Sift

Pathogenic

0.0

Vest4

0.052

MutPred

0.22

Gain of phosphorylation at C20 (P = 0.0033);

MVP

0.23

ClinPred

0.028

GERP RS

-0.073

gMVP

0.070

Splicing

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