Genetic Variant VMA21:p.Glu17Asp (chrX-151396890-G-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001363810.1(VMA21):c.51G>C(p.Glu17Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00089 in 522,449 control chromosomes in the GnomAD database, including 4 homozygotes. There are 119 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 3 hom., 79 hem., cov: 21)

Exomes 𝑓: 0.00043 ( 1 hom. 40 hem. )

Consequence

VMA21
NM_001363810.1 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0860

Variant links:

Genes affected

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:

ENSG00000287918 (HGNC:):

ENSG00000287918 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035504699).

BP6

Variant X-151396890-G-C is Benign according to our data. Variant chrX-151396890-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1690444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001363810.1 link	c.51G>C	p.Glu17Asp	missense_variant	Exon 1 of 3		NP_001350739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
VMA21	ENST00000370361.5 link	c.51G>C	p.Glu17Asp	missense_variant	Exon 2 of 4	5	ENSP00000359386.1	Q3ZAQ7-2
ENSG00000287918	ENST00000660681.2 link	n.248C>G		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000287918	ENST00000664935.1 link	n.129C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

283

AN:

110576

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

AN XY:

32804

show subpopulations

Gnomad AFR

AF:

0.00873

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00132

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:

0.0000379

Gnomad OTH

AF:

0.00135

GnomAD3 exomes

AF:

0.000507

AC:

AN:

102574

Hom.:

AF XY:

0.000348

AC XY:

AN XY:

37366

show subpopulations

Gnomad AFR exome

AF:

0.00842

Gnomad AMR exome

AF:

0.000471

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:

0.000328

GnomAD4 exome

AF:

0.000435

AC:

179

AN:

411828

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

AN XY:

151894

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.000444

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000792

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000428

Gnomad4 OTH exome

AF:

0.000733

GnomAD4 genome

AF:

0.00259

AC:

286

AN:

110621

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

AN XY:

32859

show subpopulations

Gnomad4 AFR

AF:

0.00881

Gnomad4 AMR

AF:

0.00132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000379

Gnomad4 OTH

AF:

0.00133

Alfa

AF:

0.00221

Hom.:

Bravo

AF:

0.00265

ExAC

AF:

0.000163

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

See cases

Benign:1

Sep 01, 2021

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ACMG classification criteria: BS2, BP4 -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.1

DANN

Benign

0.69

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.11

REVEL

Benign

0.028

Sift

Pathogenic

0.0

Vest4

0.057

MutPred

0.085

Loss of helix (P = 0.079);

MVP

0.29

ClinPred

0.0063

GERP RS

-0.85

gMVP

0.072

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